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Review ArticleA Survey of Modulation of Gut Microbiota byDietary Polyphenols

Montserrat Duentildeas1 Irene Muntildeoz-Gonzaacutelez2 Carolina Cueva2

Ana Jimeacutenez-Giroacuten2 Fernando Saacutenchez-Pataacuten2 Celestino Santos-Buelga1

M Victoria Moreno-Arribas2 and Begontildea Bartolomeacute2

1Grupo de Investigacion en Polifenoles Unidad de Nutricion y Bromatologıa Facultad de FarmaciaUniversidad de Salamanca Campus Miguel de Unamuno 37007 Salamanca Spain2Grupo de Biotecnologıa Enologica Aplicada Instituto de Investigacion en Ciencias de la Alimentacion (CIAL)CSIC-UAM Campus de Cantoblanco CNicolas Cabrera 9 28049 Madrid Spain

Correspondence should be addressed to Begona Bartolome bbartolomecsices

Received 9 July 2014 Revised 17 October 2014 Accepted 23 October 2014

Academic Editor Clara G de los Reyes-Gavilan

Copyright copy 2015 Montserrat Duenas et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Dietary polyphenols present in a broad range of plant foods have been related to beneficial health effects This review aims toupdate the current information about the modulation of the gut microbiota by dietary phenolic compounds from a perspectivebased on the experimental approaches used After referring to general aspects of gut microbiota and dietary polyphenols studiesrelated to this topic are presented according to their experimental design batch culture fermentations gastrointestinal simulatorsanimal model studies and human intervention studies In general studies evidence that dietary polyphenols may contribute tothe maintenance of intestinal health by preserving the gut microbial balance through the stimulation of the growth of beneficialbacteria (ie lactobacilli and bifidobacteria) and the inhibition of pathogenic bacteria exerting prebiotic-like effects Combinationof in vitro and in vivo models could help to understand the underlying mechanisms in the polyphenols-microbiota-host triangleand elucidate the implications of polyphenols on human health From a technological point of view supplementation with rich-polyphenolic stuffs (phenolic extracts phenolic-enriched fractions etc) could be an effective option to improve health benefits offunctional foods such as the case of dairy fermented foods

1 Introduction

More and more studies confirm the importance of the gutmicrobiota in host health including mental health Gutbacteria not only help us to maximize the absorption ofnutrients and energy but also are essential in the body healthstatus [1] In particular microbial infections and imbalancesin the composition of the gut microbiota are associatedwith intestinal disorders such as chronic inflammatory boweldiseases and with other immune related disorders [2 3]Although genetic and environmental factors are main deter-minants of gut microbiota composition it is well establishedthat diet influences microbial fermentation and total bacteriain the intestine In fact interindividual variation in gutmicrobiota may in part reflect differences in dietary intake

although the response of the gutmicrobiota to dietary changecan also differ among individuals [4]

Phenolic compounds or polyphenols are secondarymeta-bolites with awidespread occurrence in the plant kingdom Innature polyphenols can be classified into two major groupsflavonoids and nonflavonoids Among flavonoids variousgroups can be distinguished according to the C-heterocyclestructure flavonols flavones flavan-3-ols isoflavones fla-vanones dihydroflavonols anthocyanidins and chalcones(Figure 1) Nonflavonoid phenolics include phenolic acidshydrolysable tannins and stilbenes among others Polyphe-nols also form part of the human diet being present in abroad range of commonly consumed fruits vegetables andplant-derived products such as cocoa tea or wine A number

Hindawi Publishing CorporationBioMed Research InternationalVolume 2015 Article ID 850902 15 pageshttpdxdoiorg1011552015850902

2 BioMed Research International

Flavonols

O

OH

O

Isoflavones

O

O

Dihydroflavonols

O

OH

O

Flavanones

O

O

Chalcones

O

Flavones

O

O

O

OH

Flavan-3-ols

Anthocyanidins

OH

O+

Figure 1 Common phenolic compounds in food

of epidemiological studies have shown that the intake ofdiets rich in fruits and vegetables is inversely associated withthe risk of various chronic diseases such as coronary heartdisease specific cancers and neurodegenerative disorders[5ndash7] Indeed a range of pharmacological effects have beendemonstrated for different phenolic compoundsmdashespeciallyflavonoidsmdashthrough in vitro ex vivo and animal assays [8 9]However health effects of these compounds depend on theirbioavailability and therefore it is important to understandhow they are absorbed metabolized and eliminated from thebody in order to ascertain their in vivo actions

Modulation of gut microbiota by polyphenols has beena topic of increasing attention by the scientific communityin the last years Several studies have been carried out bydifferent authors ranging from the simplest experimentalapproaches on the effect of polyphenols on the growthof isolated intestinal bacteria to complex approximationsimplying the whole fecal microbiota either in fermentationexperiments (batch cultures and continuous simulators) orthrough compositional analysis of animal and human fecalsamplesThe existing knowledge about relationships betweenpolyphenols and gut microbiota has been object of manyreviews from different perspectives Thus some authorshave put their attention on the impact of food constituents(polyphenols included) in the gut microbiome [10 11] whileothers have focused on the effects of dietary polyphenolson microbial modulation and their potential implicationsin human health [12ndash15] Selma et al [16] wrote probablythe first review trying to put together the concepts of

microbial degradation of polyphenols and modulation ofgut microbiota by polyphenols and phenolic metabolitesThis two-way interaction between phenolics and intestinalbacteria has been also reviewed focusing on wine [17] andtea polyphenols [18] The development of improved biologyand microbial techniques has allowed notable advances inthe knowledge of the gut microbiota and their modulationby dietary components and hence polyphenolsThe potentialof the novel metabolomic approaches in the study of theimpact of polyphenols on gut microbiome has been recentlyreviewed [19]

Being aware of all this previous reviewing work we haveaimed to update the available information about modulationof gut microbiota by dietary polyphenols with a perspectivebased on the experimental approaches used After two gen-eral sections covering relevant aspects about gut microbiota(Section 2) and dietary polyphenols (Section 3) studies arepresented according to their experimental design batchculture fermentations (Section 4) gastrointestinal simulators(Section 5) animal model studies (Section 6) and humanintervention studies (Section 7) Main findings and generalconclusions generated from the different types of studies arefinally discussed (Section 8)

2 Gut Microbiota Composition and Analysis

The human gut is the natural habitat of a large diverse pop-ulation and dynamics of microorganisms mainly anaerobicbacteria which have adapted to life on mucosal surfaces

BioMed Research International 3

in the gut lumen The acquisition of gut microbiota beginsat birth and is strongly influenced by a range of factorsthat include host genetics immunological factors antibioticusage and also dietary habits [20] The microbial content ofthe gastrointestinal tract changes along its length rangingfrom a narrow diversity and low numbers of microbes inthe stomach to a wide diversity and high numbers in thelarge intestine which can reach 1012 CFUmL [21] Most ofintestinal bacteria belong to phylum Firmicutes (includingClostridium Enterococcus Lactobacillus and Ruminococcusgenera) and Bacteroidetes (including Prevotella and Bac-teroides genera) which constitute over 90 of known phy-logenetic categories and dominate the distal gut microbiota[22] Recently a novel classification of microbiota into threepredominant ldquoenterotypesrdquo dominated by three differentgenera Bacteroides Prevotella and Ruminococcus has beensuggested [23] In this line Wu et al [24] demonstratedthat long-term diet high in animal proteins and fats versussimple carbohydrates clustered the human subjects into thepreviously described enterotypes Bacteroides and PrevotellaHowever there is a current debate if the enterotypes shouldbe seen discontinuous or as a gradient [25] But in any casea common observation is that homeostasis and resilience arecoupled to a highly diverse gut microbiota in healthy peoplewhereas inflammatory and metabolic disorders are linked toperturbations in the composition andor functions of the gutmicrobiota [26]

Culture-based techniques employed to bacteria identifi-cation are fairly cheap laborious and time-consuming andgives a limited view of the diversity and dynamics of thegastrointestinal microbiota with less than 30 of gut micro-biotamembers having been cultured to date [27] Since 1990sthe introduction of novel molecular biological procedureshas made it possible to overcome some of these limitationswith the use of culture-independent methods [28] Theseprocedures are based on sequence divergences of the smallsubunit ribosomal RNA (16S rRNA) and include techniquessuch as denaturing gradient gel electrophoresis (DGGE)terminal restriction fragment length polymorphism (T-RFLP) fluorescence in situ hybridization (FISH) quantitativepolymerase chain reaction (qPCR) DNA microarrays andnext-generation sequencing (NGS) of the 16S rRNA geneor its amplicons [29] NGS techniques have promoted theemergence of new high-throughput technologies such asgenomics metagenomics transcriptomics and metatran-scriptomics Metagenomics gives a more in-depth unbiasedmicrobial analysis beyond the group level and involvesmultiple species besides showing shorter sequencing speedextended read length and lower costs [30] However theenormous amount of data generated becomes cumbersome toanalyze and requires lots of dedicated time as well as expertiseto manage [29]

In the context of polyphenol-microbiota interactions theemerging high-throughput meta-genomic transcriptomicand proteomic approaches can be adopted to identify genesand micro-organisms involved in polyphenol (in)activationand conversion to reconstruct metabolic pathways and tomonitor how microbial communities adjust their metabolic

activities upon polyphenol exposure [30] Application ofthese technologies to human fecal samples requires fur-ther investigation to determine how these samples reflectmetabolism inside the gut and ultimately to improve theunderstanding of the impact of polyphenols on host health[12 31]

3 Dietary Polyphenols

It has been estimated that 90ndash95 of dietary polyphenols arenot absorbed in the small intestine and therefore reach thecolon [32] although absorption and metabolism are largelyinfluenced by their chemical structure Most flavonoids arepoorly absorbed from the small intestine and are highlymetabolized in the large intestine Isoflavones seem to bethe best absorbed dietary flavonoids catechins flavanonesand flavonol glycosides are intermediate whereas proantho-cyanidins flavan-3-ol gallates and anthocyanins would bethe worst absorbed [33]

The first step in the metabolism of flavonoids with theexception of flavan-3-ols (ie catechins and proanthocyani-dins) is likely to be deglycosylation before absorption inthe small intestine Hydrolysis of some flavonoid glycosidemight already occur in the oral cavity as both saliva andoral microbiota show 120573-glucosidase activity But the mech-anism most usually assumed for flavonoid deglycosylation ishydrolysis by lactase phlorizin hydrolase (LPH) in the brush-border of the small intestine epithelial cells [34 35] so thatthe resulting aglycones would enter the enterocyte by passivediffusion The resulting aglycone is rapidly biotransformedby phase II enzymes within the enterocyte and further inthe liver so that conjugated metabolites (ie glucuronidesO-mehtylethers andor sulphates) through the respectiveaction of UDP-glucuronosyltransferase (UGT) catechol-O-methyltransferase (COMT) and sulphotransferases would bethe circulating forms in the human body [36 37]

Generally a relevant fraction of dietary flavonoids isnot absorbed in the small intestine and together withthe conjugated metabolites that returned to the intestinallumen via enterohepatic circulation reaches the large intes-tine where compounds are subjected to the action of thecolonic microbiota Intestinal bacteria show diverse degly-cosylating activities thus releasing aglycones that might beabsorbed in a lesser extent and more probably degradedto simpler phenolic derivatives [38 39] Degradation offlavonoid aglycones by colonic microbiota involves ring-C cleavage and reactions affecting functional groups suchas dehydroxylation demethylation or decarboxylation [39]Various hydroxylated aromatic compounds derived from theA-ring (eg phloroglucinol 34-dihydroxybenzaldehyde or34-dihydroxytoluene) and phenolic acids derived from theB-ring have been reported as relevant products of the colonictransformation of flavonoids [40] It has become evidentthat the beneficial effects attributed to dietary polyphenolsappear to be due more to phenolic metabolites formed in thegastrointestinal tract mainly derived from the action of gutbacteria rather than to the original forms found in food [41]

In subsequent sections main findings related to themodulation of gut microbiota by polyphenols are presented

4 BioMed Research International

as obtained from different methodological approaches andmicrobial analysis techniques

4 Studies Using Batch Culture Fermentations

Although in vivo human or animal intervention trials arephysiologically most relevant to study both polyphenolmetabolism and microbial modulation in vitro tools havebeen designed to simulate intestinal conditions In combi-nation with in vivo trials in vitro experiments may help toelucidate the extent bioconversion processes mediated by thehost itself [42 43] The complexity of in vitro gut models isdiverse ranging from simple static models (batch culture fer-mentation) to advanced continuous models (gastrointestinalsimulators)

Simple static gut models also known as batch-typecultures are generally closed systems using sealed bottlesor reactors containing suspensions of fecal material that aremaintained under anaerobic conditions They are relativelyeasy to operate and cost-effective have a fair throughputand allow for parallel screening This model approach isprimarily used to assess the stability of polyphenols in thepresence of human-derived gut microbiota and to evaluatewhich environmental conditions favor or limit polyphenolbioconversion However these static gut models are onlyadequate for simulating short-term conditions in the gutfor assessment of long-term adaptations of the gut microbialcommunity more complex dynamic models are needed[12]

Table 1 reports different studies of modulation of gutmicrobiota by dietary polyphenols using batch-type culturesDetails about fermentation conditions (fecal concentrationpolyphenol origin and dose and incubation time) andmicro-bial techniques used and main effects on bacteria groups(growth enhancement growth inhibition or no effect) havebeen included As general characteristics fecal fermentationsemployed feces concentration le10 (wv) and lasted 48 hmaximum Both pure phenolic compounds and phenolic-rich extracts were added to the fecal medium at a finalconcentration lt10 (wv) and changes in specific bacterialgroups weremainly assessed by FISH analysis A first relevantexperiment using batch culture fermentation was carriedout by Tzounis et al [44] who found that the flavan-3-olmonomers [(minus)-epicatechin and (+)-catechin] promoted thegrowth of Clostridium coccoides-Eubacterium rectale groupwhich is known to produce large amounts of butyrate a short-chain fatty acid (SCFA) with anti-inflammatory and anti-neoplasic properties (+)-catechin also increased the growthof Lactobacillus-Enterococcus spp Bifidobacterium spp andEscherichia coli but decreased the growth of Clostridiumhistolyticum Also using standard compounds Hidalgo et al[45] found that anthocyanins (ie malvidin-3-glucoside andamixture of anthocyanins) significantly enhanced the growthof Lactobacillus-Enterococcus spp and Bifidobacterium sppIn addition malvidin-3-glucoside showed a tendency topromote the growth of the C coccoides-E rectale group

Similar results have been observed in batch culturefermentations with phenolic-rich extracts from different

sourcesMolan et al [46] found that the addition of blueberryextracts to a mixture of fecal bacterial populations signifi-cantly increased the number of lactobacilli and bifidobacteria(Table 1) In the same line Bialonska et al [47] reportedenhancement of the growth of total bacteria Bifidobacteriumspp and Lactobacillus-Enterococcus spp in response to acommercial extract of pomegranate without influencing theC coccoides-E rectale and C histolyticum groups (Table 1)Mandalari et al [48] suggested a potential prebiotic effectfor natural and blanched almond skins as these foodstuffs infermentations with fecal microbiota significantly increasedthe populations of bifidobacteria and C coccoides-E rectalegroup and decreased the number of C hystolyticum groupThese authors related the possible prebiotic effect by almondskins not only to a high amount of dietary fibre but also tosome phenolic compounds such as ferulic acid flavan-3-olsand flavonols present in the almond skins [48] Fogliano et al[49] carried out an in vitro fermentation with a water-insoluble cocoa fraction in a three-stage continuous culturecolonicmodel system It was observed that this cocoa fractionpresented prebiotic activity producing a significant increasein lactobacilli and bifidobacteria as well as an increase inbutyrate production They concluded that the coexistenceof fermentable polysaccharides and free flavanol monomersin cocoa such as catechins might be very effective in themodification of gut microbiota Similar conclusions weredrawn by Pozuelo et al [50] who found a significant increaseof the growth of Lactobacillus reuteri and Lactobacillusacidophilus in the presence of a grape antioxidant dietary fibernaturally obtained from red grapes Our research group car-ried out several batch culture fermentations of two flavan-3-ol fractions with different degree of polymerisation and winepolyphenols with fecal microbiota from different healthyvolunteers [51 52] Both flavan-3-ol fractions promoted thegrowth ofLactobacillusEnterococcus spp and inhibited theChistolyticum group during fermentation although the effectswere only statistically significant with the less polymerizedfractionWine polyphenols only showed a slight inhibition intheC histolyticum group probably due to their lower contentin flavan-3-ols

Additionally this type of fermentations has also beenused to assess the contribution of certain probiotic strainsto the colonic metabolism of polyphenols In this senseBarroso et al [53] carried out fermentations of a red wineextract inoculated with human microbiota obtained fromthe colonic compartments of a dynamic simulator in thepresence and absence of the probiotic strain L plantarumIFPL935 Microbial analysis by qPCR indicated that redwine polyphenols induced greater variations among in vitrobatches harboring different colon-region (ascending colondescending colon and effluent) microbiota than those foundwhen L plantarum IFPL935 was added Batches inoculatedwith microbiota from the ascending colon were shown toharbor the major proportion of saccharolytic bacteria (Bac-teroides Bifidobacterium and Prevotella) whereas Clostrid-ium groups were found in major numbers in the batchesinoculated with microbiota simulating the distal regions [53](Table 1)

BioMed Research International 5

Table1Stud

iesu

singbatchcultu

referm

entatio

n

Reference

Fecal

concentration

Phenolic

compo

undfood

Dose

Timeo

fincubatio

nMicrobial

techniqu

eGrowth

enhancem

ent

Growth

inhibitio

nNoeffect

Tzou

nise

tal

(2008)

[44]

10w

v(+)-catechin

150m

gL

1000

mgL

lt48

hFISH

Lactobacillus-

Enterococcus

spp

Bifid

obacteriu

mspp

Ccoccoides-E

rectale

grou

pE

coli

Chisto

lyticum

grou

p

Molan

etal(2009)

[46]

01

vv

Blueberryextracts

510

and25

48h

FISH

Lactob

acilli

Bifid

obacteria

Bialon

skae

tal

(2010)

[47]

10w

vPo

megranate

extractand

punicalagin

10

48h

FISH

Totalbacteria

Bifid

obacteriu

mspp

Lactobacillus-

Enterococcus

spp

Ccoccoides-E

rectale

grou

pC

histo

lyticum

grou

p

Mandalarietal

(2010)

[48]

10w

vAlm

ondskins

1w

vpredigested

almon

dskins

lt24

hFISH

Bifid

obacteria

Ccoccoides-E

rectale

grou

p

Chisto

lyticum

grou

p

Fogliano

etal

(2011)[49]

5w

vWater-in

soluble

cocoafraction

1w

v36

hFISH

Bifid

obacteria

Lactob

acilli

Cuevae

tal(2013)

[51]

10w

vGrape

seed

extract

fractio

ns300ndash

450m

gL

lt48

hFISH

Lactobacillus-

Enterococcus

spp

Chisto

lyticum

grou

p

Hidalgo

etal

(2012)

[45]

10w

v

Malvidin-3-O-

glucoside

Antho

cyanidins

mixture

20mgLand

200m

gL

4850

mgLand

48500m

gL

lt24

hFISH

Lactobacillus-

Enterococcus

spp

Bifid

obacteriu

mspp

Ccoccoides-E

rectale

grou

p

Sanchez-Patanet

al(2012)[52]

1wv

Redwinee

xtract

600m

gL

48h

FISH

Chisto

lyticum

grou

p

Lactobacillus-

Enterococcus

spp

Barrosoetal

(2013)

[53]

Redwinee

xtract

500m

gL

48h

qPCR

Lactobacillus

spp

Bifid

obacteriu

mspp

Bacteroidesspp

Ru

minococcusspp

6 BioMed Research International

Table 2 Studies using the gastrointestinal simulators (ie SHIME)

Reference Simulator Phenoliccompoundfood Dose Time Microbial

techniquePopulationincrease Population decrease

De Boeveret al (2000)[57]

SHIME Soy germ powder 25 gday 2 weeks Plate count

EnterobacteriaceaeColiforms

Lactobacillus sppStaphylococcus sppClostridium spp

Kempermanet al (2013)[31]

Twin-SHIME Black tea extract

3 times dailydosing(1000mg

polyphenolsas total daily

dose)

2 weeks

Plate countqPCR

PCR-DGGEpyrosequencing

Klebsiella sppEnterococci

Akkermansia spp

BifidobacteriaBlautia coccoidesAnaeroglobus sppVictivallis spp

Kempermanet al (2013)[31]

Twin-SHIME

Red wine-grapeextract

3 times dailydosing(1000mg

polyphenolsas total daily

dose)

2 weeks

Plate countqPCR

PCR-DGGEpyrosequencing

Klebsiella sppAlistipes spp

Cloacibacillus sppVictivallis spp

Akkermansia spp

BifidobacteriaBlautia coccoides

groupAnaeroglobus spp

Subdoligranulum sppBacteroides

5 Studies Using HumanGastrointestinal Simulators

In contrast to short-duration experiments with static gutmodels longer-term experiments are required when theadaptation of the gut microbial community to dietarypolyphenols needs to be assessed To this end dynamic invitro gut models such as the ldquoReadingrdquo model [54] theSimulator of the Human Intestinal Microbial Ecosystem(SHIME) the TNO Intestinal Model 2 (TIM2) [55 56] andthe recent gastrointestinal simulator set up in our Institute(SIMGI) (unpublished work) have been developed where gutmicrobiota are cultured over a longer time frame (days toweeks) in one or multiple connected pH controlled vesselsrepresenting different parts of the gastrointestinal tract

As an example of the versatility and potential of humangastrointestinal simulators Table 2 reports a series of studiesabout modulation of gut microbiota by polyphenols usingthe SHIME [57 58]This validatedmodel comprises stomachand small intestinal sections for predigestion of food aswell as vessels stimulating the ascending transcending anddescending parts of the human colon allowing assessment ofchanges in the different colonic areas that are very challengingto access in a human intervention However it should beunderlined that this approach takes for granted that theextracts reach intact the colonic region and no nutrientabsorption is consideredThe use of the SHIME to investigatethe effects of a soy germ powder on the fermentative capacityof the simulated microbiota of the colon was the aim of astudy carried out by De Boever et al [57]They observed thatthe addition of the soy germ powder in a 2-week treatmentresulted into an overall increase of bacterial marker pop-ulations (Enterobacteriaceae coliforms Lactobacillus sppStaphylococcus spp and Clostridium spp) with a significantincrease of 2 log10 units in the Lactobacillus spp populationMore recently Kemperman et al [31] using the twin-SHIME

model studied the influence of a bolus dose and a 2-weekcontinuous administration of complex dietary polyphenolsfrom black tea or red wine grape extracts on the colonicmicrobiota The Twin-SHIME system involving two modelsthat run in parallel was inoculatedwith the same fecal samplefor direct comparison of the effect of the two polyphenoltypes A combination of analyses including cultivation PCR-denaturing gradient gel electrophoresis (DGGE) quantita-tive PCR and high throughput pyrosequencing of the 16Sribosomal RNA gene was applied to characterize micro-bial community changes This study showed that complexpolyphenols in the context of a model system can modulateselect members of the human gut microbiota revealing noveltargets potentially involved in polyphenolmetabolism andorresistant microbes to be further investigated for polyphenolmetabolism or resistance mechanisms [31]

6 Animal Models Studies

It is widely assumed that preliminary evidence should bewarranted in animal models before human interventiontrials Animal models contribute to better understanding themechanisms and biological effects that could be likely tohappen in the human body The metabolism of polyphenolshas been object of numerous animal studies (mostly inrodents) especially for their impact on metabolic disorders[58] but only a few of these studies have followed thedynamics and composition of the intestinal microbiota inassociation with polyphenol metabolites retrieved from thehost Caution is required in extrapolating results to humansbecause culture-independent comparisons have revealed thatmost bacterial genera and species found in mice are not seenin humans although the distal gut microbiota of mice andhumans harbors the same bacterial phyla [59] In this sectionstudies performed in animals in order to assess the effects ofpolyphenols on the modulation of intestinal microbiota are

BioMed Research International 7

Table 3 Animal model studies

Reference Animal Phenoliccompoundfood Dose Treatment

durationMicrobialtechnique Population increase Population decrease

Hara et al(1995) [60] Pigs Tea polyphenols 02 (free access) 2 weeks Plate count Lactobacilli

Total bacteriaBacteroidaceaeC perfringens

Ishihara et al(2001) [61] Calves Green tea extracts 15 gday 4 weeks Plate count

Bifidobacterium sppLactobacillus sppC perfringens

Smith andMackie (2004)[66]

Rats

Proantocyanidinsextracted from

Acaciaangustissima

07 (low tannindiet) and 20

(high tannin diet)

35 weekstreatment +35 weekswashout

PCR-DGGEDot blot

hybridization

Bacteroides fragilisgroup

Bacteroides-Prevotella-

Porphyromonas group

Enterobacteriaceae

C leptum group

Dolara et al(2005) [62] Rats

Red winepolyphenolspowder

50mgkg 16 weeks Plate count LactobacilliBifidobacteria

PropionibacteriaBacteroidesClostridia

Sembries et al(2006) [63] Rats Apple juice free access 4 weeks Plate count Lactobacilli

BifidobacteriaSembries et al(2003) [64] Rats Apple pomace

juice colloid5 suppl diet(free access) 6 weeks Plate count

FISH Bacteroidaceae

Larrosa et al(2009) [68] Rats Resveratrol 1mgkgday 25 days Plate count Lactobacilli

Bifidobacteria

Molan et al(2010) [69] Rats

Blackcurrantextracts (leaf or

berry)

3 timesweek(i) 30mgkg

(leaf)(ii) 134mgkg

(berry)

4 weeks FISH

Lactobacilli (berryextract)

Bifidobacteria (leafand berry extracts)

Viveros et al(2011) [65]

Broilerchicks

Grape pomaceconcentrate(GPC) Grapeseed extract

(GSE)

60 gkg diet(GPC)

72 gkg diet(GSE)

(free access)

21 days Plate countT-RFLP

E coliEnterococcus sppLactobacillus spp

Lacombe et al(2013) [70] Rats Lowbush wild

blueberries

20 g feedday(eq 24 plusmn 52mganthocyaninday)

6 weeks Metagenomicsequencing

Thermonospora sppCorynebacteria spp

Slackia spp

Lactobacillus sppEnterococcus spp

summarized (Table 3) Experiments were mainly performedin rats although other larger animals such as chicks calvesor pigs have also been used Gut microbial communities wereevaluated by diverse methodologies including culture-basedmethods (plate count) DGGE FISH T-RFLP qPCR andmetagenomic sequencing

Animal studies performed in pigs [60] and in calves[61] demonstrated that tea polyphenols administration con-tributed to the improvement in the composition of the intesti-nal microbiota Thus the administration of tea polyphenolsin pigs significantly increased the levels of lactobacilli whilstit diminished the levels of total bacteria and Bacteroidaceaeand a tendency to decrease in lecithinase positive clostridiaincludingC perfringenswas also observed [60] However thereduction rate of Bifidobacterium spp and Lactobacillus sppwas slowwhile that ofC perfringensdecreased faster in calvessupplemented with the green tea extract [61]

Dolara et al [62] showed that treatment with winepolyphenols in carcinogen-treated F344 rats was associated

with a strong variation in the colonic microbiota comparedto the control-fed rats Although the total bacterial counts andanaerobeaerobe ratio of microorganisms in the feces frompolyphenol-treated rats were similar to that from control ratspropionibacteria Bacteroides and Clostridia decreased whilelactobacilli and bifidobacteria increased Based on additionalexperiments these authors concluded that reduction ofoxidative damage modulation of colonic flora and variationin gene expression may be all connected in the action of winepolyphenols on the intestinal function and carcinogenesis

In other study rats fedwith apple juice instead of drinkingwater showed more lactobacilli and bifidobacteria in freshfeces that differed from the controls by one-log10 colonyforming units [63] The same research group studied theeffect of colloids isolated from apple pomace extraction juiceson the intestinal microbiota in Wistar rats An increaseof Bacteroidaceae in almost one-log10 higher counts wasobserved in feces of rats fed with apple juice colloid thancontrol rats [64] Another animal experiment conducted to

8 BioMed Research International

study the effect on intestinal microbiota of the inclusionof grape pomace extracts in the diet of broiler chicks [65]found that for the cecum birds fed grape extracts had higherpopulations of E coli Lactobacillus and Enterococcus speciesthan birds in any other treatment group These authorsconcluded that grape polyphenol-rich products modified thegut morphology and intestinal microbiota and increased thebiodiversity degree of intestinal bacteria in broiler chicks

Inclusion of condensed tannins (proanthocyanidins)extracted from Acacia angustissima on rat diet resulted ina shift in the predominant bacteria towards tannin-resistantGram-negative Enterobacteriaceaeand Bacteroides speciesand reduced the number of Gram-positive C leptum group[66] Compatible results were obtained in an experimentwith rats fed a proanthocyanidin-rich cocoa preparation [67]where the authors found a significant decrease in the propor-tion of Bacteroides Clostridium and Staphylococcus generain the feces of cocoa-fed animals Interestingly reductions inClostridium species were found to correlate with weight lossand decrease in body mass index

Larrosa et al [68] observed an increase in lactobacilliand bifidobacteria when resveratrol (3541015840-trihydroxy-trans-stilbene) which naturally occurs in grapes and grape-derivedfoodstuffs such as red wine was administered to rats Afterinduction of colitis by dextran sulphate sodium proliferationof both E coli and enterobacteria was lower in rats treatedwith resveratrol than in control rats This could be the resultof an indirect effect of resveratrol-supplemented diet whichincreased bifidobacteria and lactobacilli counts preventingthe colonization and invasion of tissues by enterobacteriaincluding E coli

Prebiotic activity of wild blackcurrant extracts observedin in vitro experiments was further confirmed in rats byMolan et al [69] A significant increase in the populationsize of lactobacilli and bifidobacteria was observed after dailyadministration of those extracts to rats Similarly a grapeantioxidant dietary fibre preparation was found to increasethe population of Lactobacillus spp when fed to rats whereaspopulations of Bifidobacterium spp decreased and changes inE coli and Bacteroides vulgatus counts were not significant[50]

Recently Lacombe et al [70] studied the composition andfunctional potential of the colon microbiota from rats feda diet enriched in lowbush wild blueberries Application ofnovel metagenomic techniques (Illumina shotgun sequenc-ing) revealed a significant reduction in the relative abundanceof the genera Lactobacillus and Enterococcus associated withwild blueberries intake In addition hierarchical analysisshowed a significant increase in the relative abundanceof the phylum Actinobacteria the order Actinomycetalesand several novel genera under the family Bifidobacteri-aceae and Coriobacteriaceae in the blueberries group Theauthors indicated that although the microbiome of ratsdiffers from humans the applied model was a powerfultool to study population dynamics and related metabolicfunctions Metagenomic studies can determine microbialcommunity profiles gene presenceabsence and abundanceand functional repertoire however they can only infer an

observed phenotype since a gene presence does not imply itsexpression or functionality [71]

7 Human Intervention Studies

Investigations involving the use of humans potentially pro-vide the best models for studying the interactions of foodcomponents (eg polyphenols) with microbiota although invivo intervention trials hold inevitable practical and ethicallimitations [12] The use of cross-over designs where volun-teers serve as their own control permits multilevel analysisschemes that increase power but requires a relevant numberof volunteers to allow for statistically significant multivariatemodels [72] Up to now only a few studies have examinedthe in vivo impact of dietary polyphenols on the humangut microbiota and most of them were focused on singlepolyphenol molecules and selected bacterial populations Asummary of human intervention studies about effects ofpolyphenols in the modulation of the intestinal microbiotais collected in Table 4 In these studies the polyphenol doseused was much dependent on the type of food preparationand its concentration normally ranging from 01 to 4 thetreatment time was also variable from 10 days to 2 monthsand the applied microbial techniques were diverse (platecount DGGE FISH T-RFLP and qPCR)

In a study with a reduced number of subjects (119899 =8) Okubo et al [73] reported a notably increase in thepercentages of Bifidobacterium spp in total fecal countsafter an intervention with a product containing 70 of teapolyphenols A significant decrease of C perfringens andother Clostridium spp was also observed during the intakeperiod However in a crossover feeding study (number ofvolunteers not reported) that investigated the effects of blacktea drinking on hypercholesterolemic volunteers Mai et al[74] found that although specific bacterial groups were notaffected the total amount of bacteria significantly decreasedhighlighting large interindividual variations More recentlyan intervention study (119899 = 10) by Jin et al [75] confirmedan overall tendency for the proportion of bifidobacteria toincrease because of green tea consumption even thoughthere were interindividual differences in the Bifidobacteriumspecies

Yamakoshi et al [76] showed that administration of aproanthocyanidin-rich extract from grape seeds to healthyvolunteers (119899 = 9) significantly increased the fecal number ofBifidobacterium whereas the number of putrefactive bacteriasuch as enterobacteria tended to decrease The interactionbetween proanthocyanidins and intestinal bacteria was alsoconfirmed in a randomized double-blind crossover andcontrolled intervention study (119899 = 22) ingesting two cocoadrinks exhibiting low and high polyphenol content [77]Compared with the consumption of the low-flavan-3-olcocoa drink the daily consumption of the high-flavan-3-ol cocoa drink significantly increased the bifidobacteria andlactobacilli populations but significantly decreased clostridiacounts

Queipo-Ortuno et al [78] performed a randomizedcrossover and controlled trial (119899 = 10) consisting of theintake of red wine dealcoholized red wine and gin over

BioMed Research International 9

Table4Hum

aninterventio

nstu

dies

Reference

Volunteer

number

Phenolic

compo

undfood

Dose

Treatm

ent

duratio

nMicrobial

techniqu

ePo

pulatio

nincrease

Popu

latio

ndecrease

Noeffect

Oku

boetal

(1994)[73]

8Green

tea

(Sun

phenon

)04g

3tim

esper

day

4weeks

Platec

ount

Cperfr

ingens

Clostridium

spp

Yamakoshi

etal(2001)[76]

9Proantocyanidin-

richextractfrom

grapes

eeds

05g

day

6weeks

Platec

ount

Bifid

obacteriu

mspp

Enterobacteriaceae

Maietal

(200

4)[74]

15Blacktea

700m

gteas

olids5

times

perd

ay21

days

FISH

DGGE

Totalbacteria

Nochanges

Claveletal

(2005)

[83]

39Isofl

avon

es100m

gday

2mon

ths

TTGEFISH

Ccoccoides-E

rectale

grou

pBifid

obacteriu

mspp

Lactobacillus-

Enterococcus

spp

Faecalibacteriu

mprau

snitziisubgroup

Costabileetal

(2008)

[84]

31Who

legrainwheat

cereals

48gday

3weeks

FISH

Bifid

obacteria

Lactob

acilli

Totalbacteria

Bacteroidesspp

C

histo

lyticum

perfringens

grou

pAc

etobacteriu

mspp

Jaqu

etetal

(200

9)[87]

16Coff

ee3cupsday

3weeks

FISH

DGGE

Bifid

obacteriu

mspp

Carvalho

-Wellsetal

(2010)

[85]

32Who

legrainmaize

cereals

48gday

3weeks

FISH

Bifid

obacteria

Totalbacteria

Bacteroidesspp

C

histo

lyticum

perfringens

grou

pAc

etobacteriu

mspp

Gill

etal

(2010)

[80]

10Ra

spberrypu

ree

20gday

4days

PCR-DGGE

Nochangesinthep

rofileo

fcolonicb

acteria

Shinoh

arae

tal(2010)[79]

8Ap

ples

2applesday

2weeks

Platec

ount

Lactobacillus

spp

Streptococcusspp

En

terococcus

spp

Enterobacteriaceae

lecithinase-po

sitive

clostrid

iainclu

ding

Cperfr

ingens

Pseudomonas

spp

10 BioMed Research International

Table4Con

tinued

Reference

Volunteer

number

Phenolic

compo

undfood

Dose

Treatm

ent

duratio

nMicrobial

techniqu

ePo

pulatio

nincrease

Popu

latio

ndecrease

Noeffect

Tzou

nise

tal

(2011)[77]

22Cocoa

flavano

l494m

gday

29mgday

4weeks

FISH

Bifid

obacteriu

mspp

Lactobacillus

spp

Chisto

lyticum

perfringens

grou

p

Vend

ramee

tal(2011)[81]

15Wild

blueberry

drink

25gwild

blueberriesd

ay6weeks

qPCR

Bifid

obacteriu

mspp

Lacidophilus

Bacteroidesspp

Prevotellaspp

Enterococcus

spp

Ccoccoides

Queipo-

Ortun

oetal

(2012)

[78]

10Re

dwine

272m

Lday

20days

qPCR

Enterococcus

spp

Prevotellaspp

Bacteroides

Bifid

obacteriu

mspp

Bacteroidesu

niform

isEggerthella

lenta

Blautia

coccoides-E

rectaleg

roup

Clostridium

spp

Chisto

lyticum

group

Actin

obacteria

Jinetal(2012)

[75]

10Green

tea

1000

mLday

10days

T-RF

LPqP

CRBifid

obacteriu

mspp

Gug

lielm

ettiet

al(2013)[82]

15Wild

blueberries

drink

25gwild

blueberriesd

ay6weeks

qPCR

Blongum

subspinfantis

Cuervo

etal

(2014)

[86]

38

Dairy

prod

ucts

Fruits

Vegetables

Cereals

Food

intake

was

recorded

usingan

annu

alfood

frequ

ency

questio

nnaire

qPCR

Lactobacillus

Bcoccoides

Clep

tum

BioMed Research International 11

three consecutive periods After the red wine period thebacterial concentrations of proteobacteria fusobacteria Fir-micutes and Bacteroidetes markedly increased comparedwith the washout period significant increases in the num-ber of Bifidobacterium spp and Prevotella spp were alsoobserved However Lactobacillus spp Clostridium spp andC histolyticum group concentrations remained unchangedthroughout the study

In a small-scale observational study (119899 = 8) Shinoharaet al [79] found that the number of bifidobacteria in fecessignificantly increased during apple intake and the numbersof Lactobacillus spp Streptococcus spp and Enterococcusspp tended to increase On the contrary enterobacteriaand lecithinase-positive clostridia including C perfringensand Pseudomonas species tended to decrease Howeverthat study did not use culture-independent microbiologytechniques and suffered from the lack of a control groupAlso in relation to fruits another small human interventionstudy (119899 = 10) with raspberry puree [80] did not observestatistically significant alterations in the profile of colonicbacteria probably due to high interindividual variation infecal bacteria although the profiles of microbial metabolitesof raspberry polyphenols varied greatly between individualsindicating that the type of gut microbiota affects cataboliteprofiles released by bacteria in the colonThis lack of effect onthe intestinal microbiota after the intake of raspberry pureemight also be due to the short duration of the treatment aswell as the techniques employed to quantify the intestinalmicrobiota

Vendrame et al [81] studied the potential prebioticactivity of a drink elaborated fromwild blueberries especiallyrich in anthocyanins in a small intervention trial (119899 = 15) Asignificant increase in Bifidobacterium spp and L acidophilusgroup was detected while no significant differences wereobserved for Bacteroides spp Prevotella spp Enterococcusspp and C coccoides In a further paper of the same group[82] seven different intragenus bifidobacteria taxonomicclusters that were among the most common and abundantbifidobacteria species inhabiting the human gutwere targetedin the same samples It was found thatB adolescentisB breveB catenulatumpseudocatenulatum and B longum subsplongumwere always present in the group of subjects enrolledwhereas B bifidum and B longum subsp infantis were notIn spite of the large interindividual variability a significantincrease of B longum subsp infantis cell concentration wasobserved in the feces of volunteers after the wild blueberrydrink treatment which was attributed to the presence ofprebiotic (bifidogenic) molecules from blueberries possiblyfibers and glycosylated anthocyanins

In a study with postmenopausal women (119899 = 39)Clavel et al [83] found that isoflavone supplementationstimulated dominant microorganisms of the C coccoides-Erectale cluster Lactobacillus-Enterococcus group Faecalibac-terium prausnitzii subgroup and Bifidobacterium genus Itwas also suggested that the concentration of C coccoides-Erectale cluster was related to women capacity to excrete equolan intestinal metabolite from daidzein In two interventionstudies with whole grain breakfast cereals from wheat (119899 =31) and maize (119899 = 32) [84 85] the ingestion of both

products resulted in significant increases in fecal bifidobac-teria andor lactobacilli without changing the relative abun-dance of other dominant members of the gut microbiotaLittle or no changes were observed in the numbers of totalbacteria Bacteroides spp C histolyticumperfringens groupand Acetobacterium spp present in the feces However aswhole grains are good sources of dietary fiber it is difficult toascribe the observed effects only to the phenolic compoundspresent in these foods In this respect Cuervo et al [86] haverecently studied the correlations between the intake of fiberand polyphenols from diet and fecal microbiota compositionin a cohort of apparently healthy subjects Results showedthat the intake of soluble pectins and flavanones fromorangespresented a negative correlation with the levels of B coccoidesand C leptum By contrast the intake of white breadproviding hemicellulose and resistant starch was directlycorrelated with Lactobacillus

Finally another human trial (119899 = 16) carried out byJaquet et al [87] assessed the impact of a moderate con-sumption of instant coffee on the general composition ofthe human intestinal bacterial population Coffee bever-ages contain significant amounts of soluble fibre (mainlygalactomannans and arabinogalactan-proteins) and phenoliccompounds (chlorogenic acids) which arewell utilised by thehuman fecal microbiota It was observed that although fecalprofiles of the dominant microbiota were not significantlyaffected after the consumption of the coffee the populationof Bifidobacterium spp increased being the largest increaseobserved for those volunteers showing the lowest initialbifidobacteria levels

8 Conclusions

This review has tried to summarize the current knowledgein relation to the phenolic metabolism by gut microbiota andthemodulation of the gutmicrobiota by phenolic compoundsand polyphenol-rich dietary sourcesThere are evidences thatthe beneficial effects attribute to dietary polyphenols dependon their biotransformation by the gut microbiota Thereforeit is important to investigate the bacterial species impli-cated in the metabolism of dietary polyphenols and furtherresearch is still needed in relation to the resultant microbialmetabolites to ascertain their mechanisms of action Onthe other hand a great number of in vitro and in vivo (inanimals andhumans) studies showing the influence of dietarypolyphenols on gut-inhabiting bacteria have been publishedin recent years Although in vitro assays facilitate experimen-tation caution must be taken in extrapolating results to invivo situation as many factors are acting upon this processIn general in both in vitro and in vivo studies polyphenols orpolyphenol-rich sources have shown to influence the relativeabundance of different bacterial groups within the gut micro-biota reducing numbers of potential pathogens including Cperfringens and C histolyticum and certain Gram-negativeBacteroides spp and enhancing mainly beneficial Clostridiabifidobacteria and lactobacilli A better understanding of theinteraction between dietary polyphenols and gut microbiotathrough the emerging advances in high-throughput meta-genomic transcriptomic and proteomic approaches would

12 BioMed Research International

be essential in order to identify genes and micro-organismsinvolved in polyphenol (in)activation and conversion andthus to elucidate the implications of diet on the modulationof microbiota for delivering health benefits

Functional foods are considered to enhance the protectiveeffects against diseases derived from some food componentsIn the last decades dairy fermented foods have probablybeen one of the most-developed functional products andhave deserved intensive research In this expansion dairyfermented foods have been supplemented with fruits cerealsand other stuffs of plant origin all of which represent a highpercentage of the current market of the dairy industry Theseproducts have a healthy appeal which attracts consumersThus fruit juicesconcentrates and prepared fruits (in theform of pieces pulp and even flour) have been successfullyincorporated in dairy fermented foods as sources of prebioticfibers and phytochemicals Among these phytochemicalspresent in plant-derived foods polyphenols have gainedmuch interest due to their diverse potential beneficial effectsin human health The supplementation of dairy fermentedproducts with rich-polyphenolic stuffs (phenolic extractsphenolic-enriched fractions etc) seems to be an effectivetechnological option to improve the benefits of these productsin the balance of the intestinal microbiota due not only to theaction of the probiotics but also to the potential modulationeffects exerted by polyphenols as it has been described in thisreview Further research in this area will aim to accomplishthe benefits of both probiotic strains and polyphenols inrelation to gut health

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors of this review were funded by the SpanishMINECO through different projects (AGL2012-40172-C02-01 AGL2010-17499 and BFU2012-35228) and the CON-SOLIDER INGENIO 2010 programme (project FUN-C-FOOD CSD2007-063) as well as Comunidad de Madrid(project ALIBIRD P2009AGR-1469) Montserrat Duenaswould like to thank the Spanish ldquoRamon y Cajalrdquo Programmefor a contract

References

[1] S E Power P W OrsquoToole C Stanton R P Ross and GF Fitzgerald ldquoIntestinal microbiota diet and healthrdquo BritishJournal of Nutrition vol 111 no 3 pp 387ndash402 2014

[2] PDeCruz L Prideaux JWagner et al ldquoCharacterization of thegastrointestinal microbiota in health and inflammatory boweldiseaserdquo Inflammatory Bowel Diseases vol 18 no 2 pp 372ndash390 2012

[3] A Kramer S Bekeschus B M Broker H Schleibinger BRazavi and O Assadian ldquoMaintaining health by balancingmicrobial exposure and prevention of infection the hygienehypothesis versus the hypothesis of early immune challengerdquoJournal of Hospital Infection vol 83 no 1 pp S29ndashS34 2013

[4] M Rescigno ldquoIntestinal microbiota and its effects on theimmune systemrdquo Cellular Microbiology vol 16 no 7 pp 1004ndash1013 2014

[5] M G L Hertog E J M Feskens P C H HollmanM B Katanand D Kromhout ldquoDietary antioxidant flavonoids and risk ofcoronary heart disease the Zutphen Elderly StudyrdquoThe Lancetvol 342 no 8878 pp 1007ndash1011 1993

[6] I C W Arts and P C H Hollman ldquoPolyphenols and diseaserisk in epidemiologic studiesrdquoThe American Journal of ClinicalNutrition vol 81 no 1 pp 317Sndash325S 2009

[7] D del Rio A Rodriguez-Mateos J P E Spencer M TognoliniG Borges and A Crozier ldquoDietary (poly)phenolics in humanhealth structures bioavailability and evidence of protectiveeffects against chronic diseasesrdquo Antioxidants amp Redox Signal-ing vol 18 no 14 pp 1818ndash1892 2013

[8] F Perez-Vizcaino and J Duarte ldquoFlavonols and cardiovasculardiseaserdquo Molecular Aspects of Medicine vol 31 no 6 pp 478ndash494 2010

[9] J P E Spencer K Vafeiadou R J Williams and D VauzourldquoNeuroinflammation modulation by flavonoids and mecha-nisms of actionrdquo Molecular Aspects of Medicine vol 33 no 1pp 83ndash97 2012

[10] J M Laparra and Y Sanz ldquoInteractions of gut microbiota withfunctional food components and nutraceuticalsrdquo Pharmacolog-ical Research vol 61 no 3 pp 219ndash225 2010

[11] X He M L Marco and C M Slupsky ldquoEmerging aspects offood and nutrition on gut microbiotardquo Journal of Agriculturaland Food Chemistry vol 61 no 40 pp 9559ndash9574 2013

[12] D Hervert-Hernandez and I Goni ldquoDietary polyphenols andhuman gut microbiota a reviewrdquo Food Reviews Internationalvol 27 no 2 pp 154ndash169 2011

[13] K M Tuohy L Conterno M Gasperotti and R Viola ldquoUp-regulating the human intestinal microbiome using whole plantfoods polyphenols andor fiberrdquo Journal of Agricultural andFood Chemistry vol 60 no 36 pp 8776ndash8782 2012

[14] U Etxeberria A Fernandez-Quintela F I Milagro L AguirreJ A Martınez and M P Portillo ldquoImpact of polyphenols andpolyphenol-rich dietary sources on gut microbiota composi-tionrdquo Journal of Agricultural and Food Chemistry vol 61 no 40pp 9517ndash9533 2013

[15] F Cardona C Andres-Lacueva S Tulipani F J Tinahonesand M I Queipo-Ortuno ldquoBenefits of polyphenols on gutmicrobiota and implications in human healthrdquo Journal ofNutritional Biochemistry vol 24 no 8 pp 1415ndash1422 2013

[16] M V Selma J C Espın and F A Tomas-Barberan ldquoInteractionbetween phenolics and gut microbiota role in human healthrdquoJournal of Agricultural and Food Chemistry vol 57 no 15 pp6485ndash6501 2009

[17] T RequenaMMonagasM A Pozo-Bayon et al ldquoPerspectivesof the potential implications ofwine polyphenols on humanoraland gut microbiotardquo Trends in Food Science amp Technology vol21 no 7 pp 332ndash344 2010

[18] J Van Duynhoven E E Vaughan F van Dorsten et alldquoInteractions of black tea polyphenols with human gut micro-biota implications for gut and cardiovascular health1-4rdquo TheAmerican Journal of Clinical Nutrition vol 98 no 6 pp 1631Sndash1641S 2013

[19] SMoco F-P JMartin and S Rezzi ldquoMetabolomics view on gutmicrobiome modulation by polyphenol-rich foodsrdquo Journal ofProteome Research vol 11 no 10 pp 4781ndash4790 2012

BioMed Research International 13

[20] R K Buddington and P T Sangild ldquoCompanion animalssymposium development of the mammalian gastrointestinaltract the resident microbiota and the role of diet in early liferdquoJournal of Animal Science vol 89 no 5 pp 1506ndash1519 2011

[21] K Tiihonen A C Ouwehand and N Rautonen ldquoHumanintestinal microbiota and healthy ageingrdquo Ageing ResearchReviews vol 9 no 2 pp 107ndash116 2010

[22] D Mariat O Firmesse F Levenez et al ldquoThe firmicutesbacteroidetes ratio of the human microbiota changes with agerdquoBMCMicrobiology vol 9 article 123 2009

[23] M Arumugam J Raes E Pelletier et al ldquoEnterotypes of thehuman gutmicrobiomerdquoNature vol 473 no 7346 pp 174ndash1802011

[24] G D Wu J Chen C Hoffmann et al ldquoLinking long-termdietary patterns with gut microbial enterotypesrdquo Science vol334 no 6052 pp 105ndash108 2011

[25] I B JefferyM J Claesson PWOrsquoToole and F Shanahan ldquoCat-egorization of the gut microbiota enterotypes or gradientsrdquoNature Reviews Microbiology vol 10 no 9 pp 591ndash592 2012

[26] WM de Vos andM Nieuwdorp ldquoGenomics a gut predictionrdquoNature vol 498 no 7452 pp 48ndash49 2013

[27] P B Eckburg E M Bik C N Bernstein et al ldquoMicrobiologydiversity of the human intestinal microbial florardquo Science vol308 no 5728 pp 1635ndash1638 2005

[28] E G Zoetendal C T Collier S Koike R I Mackie and H RGaskins ldquoMolecular ecological analysis of the gastrointestinalmicrobiota a reviewrdquo Journal of Nutrition vol 134 no 2 pp465ndash472 2004

[29] M H Fraher PW OrsquoToole and E MM Quigley ldquoTechniquesused to characterize the gut microbiota a guide for the clini-cianrdquo Nature Reviews Gastroenterology and Hepatology vol 9no 6 pp 312ndash322 2012

[30] R A Kemperman S Bolca L C Roger and E E VaughanldquoNovel approaches for analysing gut microbes and dietarypolyphenols challenges and opportunitiesrdquo Microbiology vol156 no 11 pp 3224ndash3231 2010

[31] R A Kemperman G Gross S Mondot et al ldquoImpact ofpolyphenols from black tea and red winegrape juice on a gutmodel microbiomerdquo Food Research International vol 53 no 2pp 659ndash669 2013

[32] M N Clifford ldquoDiet-derived phenols in plasma and tissues andtheir implications for healthrdquo Planta Medica vol 70 no 12 pp1103ndash1114 2004

[33] A Crozier D del Rio and M N Clifford ldquoBioavailability ofdietary flavonoids and phenolic compoundsrdquoMolecular Aspectsof Medicine vol 31 no 6 pp 446ndash467 2010

[34] A J Day M S Dupont S Ridley et al ldquoDeglycosylation offlavonoid and isoflavonoid glycosides by human small intestineand liver beta-glucosidase activityrdquo FEBS Letters vol 436 no 1pp 71ndash75 1998

[35] A J Day F J Canada J C Dıaz et al ldquoDietary flavonoid andisoflavone glycosides are hydrolysed by the lactase site of lactasephlorizin hydrolaserdquo FEBS Letters vol 468 no 2-3 pp 166ndash1702000

[36] A Scalbert and G Williamson ldquoDietary intake and bioavail-ability of polyphenolsrdquo Journal of Nutrition vol 130 no 8 pp2073Sndash2085S 2000

[37] A R Rechner G Kuhnle H Hu et al ldquoThe metabolism ofdietary polyphenols and the relevance to circulating levels ofconjugated metabolitesrdquo Free Radical Research vol 36 no 11pp 1229ndash1241 2002

[38] A-M Aura K A OrsquoLeary G Williamson et al ldquoQuercetinderivatives are deconjugated and converted to hydroxypheny-lacetic acids but not methylated by human fecal flora in vitrordquoJournal of Agricultural and Food Chemistry vol 50 no 6 pp1725ndash1730 2002

[39] A-M Aura ldquoMicrobial metabolism of dietary phenolic com-pounds in the colonrdquo Phytochemistry Reviews vol 7 no 3 pp407ndash429 2008

[40] M Monagas M Urpi-Sarda F Sanchez-Patan et al ldquoInsightsinto themetabolism andmicrobial biotransformation of dietaryflavan-3-ols and the bioactivity of their metabolitesrdquo Food andFunction vol 1 no 3 pp 233ndash253 2010

[41] GWilliamson andMNClifford ldquoColonicmetabolites of berrypolyphenols the missing link to biological activityrdquo BritishJournal of Nutrition vol 104 no 3 pp S48ndashS66 2010

[42] D M Jacobs E Gaudier J van Duynhoven and E E VaughanldquoNon-digestible food ingredients colonic microbiota and theimpact on gut health and immunity a role for metabolomicsrdquoCurrent Drug Metabolism vol 10 no 1 pp 41ndash54 2009

[43] S Bolca S Possemiers V Maervoet et al ldquoMicrobial anddietary factors associatedwith the 8-prenylnaringenin producerphenotype a dietary intervention trial with fifty healthy post-menopausal Caucasian womenrdquo British Journal of Nutritionvol 98 no 5 pp 950ndash959 2007

[44] X Tzounis J Vulevic G G C Kuhnle et al ldquoFlavanolmonomer-induced changes to the human faecal microflorardquoBritish Journal of Nutrition vol 99 no 4 pp 782ndash792 2008

[45] M Hidalgo M J Oruna-Concha S Kolida et al ldquoMetabolismof anthocyanins by human gut microflora and their influenceon gut bacterial growthrdquo Journal of Agricultural and FoodChemistry vol 60 no 15 pp 3882ndash3890 2012

[46] A L Molan M A Lila J Mawson and S De ldquoIn vitroand in vivo evaluation of the prebiotic activity of water-soluble blueberry extractsrdquo World Journal of Microbiology andBiotechnology vol 25 no 7 pp 1243ndash1249 2009

[47] D Bialonska P Ramnani S G Kasimsetty K R Muntha GR Gibson and D Ferreira ldquoThe influence of pomegranate by-product and punicalagins on selected groups of human intesti-nal microbiotardquo International Journal of FoodMicrobiology vol140 no 2-3 pp 175ndash182 2010

[48] G Mandalari R M Faulks C Bisignano K W Waldron ANarbad and M S J Wickham ldquoIn vitro evaluation of theprebiotic properties of almond skins (Amygdalus communisL)rdquoFEMS Microbiology Letters vol 304 no 2 pp 116ndash122 2010

[49] V Fogliano M L Corollaro P Vitaglione et al ldquoIn vitro bioac-cessibility and gut biotransformation of polyphenols present inthe water-insoluble cocoa fractionrdquoMolecular Nutritionamp FoodResearch vol 55 supplement 1 pp S44ndashS55 2011

[50] M J Pozuelo A Agis-Torres D Hervert-Hernandez etal ldquoGrape antioxidant dietary fiber stimulates Lactobacillusgrowth in rat cecumrdquo Journal of Food Science vol 77 no 2 ppH59ndashH62 2012

[51] C Cueva F Sanchez-Patan M Monagas et al ldquoIn vitrofermentation of grape seed flavan-3-ol fractions by humanfaecal microbiota changes in microbial groups and phenolicmetabolitesrdquo FEMSMicrobiology Ecology vol 83 no 3 pp 792ndash805 2013

[52] F Sanchez-Patan C CuevaMMonagas et al ldquoIn vitro fermen-tation of a red wine extract by human gut microbiota changesin microbial groups and formation of phenolic metabolitesrdquoJournal of Agricultural and Food Chemistry vol 60 no 9 pp2136ndash2147 2012

14 BioMed Research International

[53] E Barroso F Sanchez-Patan P J Martın-Alvarez et al ldquoLacto-bacillus plantarum IFPL935 favors the initial metabolism of redwine polyphenols when added to a colonic microbiotardquo Journalof Agricultural and Food Chemistry vol 61 no 42 pp 10163ndash10172 2013

[54] G R Gibson J H Cummings and G T Macfarlane ldquoUse ofa three-stage continuous culture system to study the effect ofmucin on dissimilatory sulfate reduction and methanogenesisby mixed populations of human gut bacteriardquo Applied andEnvironmentalMicrobiology vol 54 no 11 pp 2750ndash2755 1988

[55] KMollyMVandeWoestyne andWVerstraete ldquoDevelopmentof a 5-step multi-chamber reactor as a simulation of thehuman intestinal microbial ecosystemrdquo Applied Microbiologyand Biotechnology vol 39 no 2 pp 254ndash258 1993

[56] M Minekus M Smeets-Peeters A Bernalier et al ldquoAcomputer-controlled system to simulate conditions of thelarge intestine with peristaltic mixing water absorption andabsorption of fermentation productsrdquoAppliedMicrobiology andBiotechnology vol 53 no 1 pp 108ndash114 1999

[57] PDeBoever BDeplancke andWVerstraete ldquoFermentation bygut microbiota cultured in a simulator of the human intestinalmicrobial ecosystem is improved by supplementing a soygermpowderrdquo Journal of Nutrition vol 130 no 10 pp 2599ndash26062000

[58] C S Yang X Wang G Lu and S C Picinich ldquoCancerprevention by tea animal studies molecular mechanisms andhuman relevancerdquoNature Reviews Cancer vol 9 no 6 pp 429ndash439 2009

[59] R E Ley F Backhed P Turnbaugh C A Lozupone R DKnight and J I Gordon ldquoObesity alters gut microbial ecologyrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 102 no 31 pp 11070ndash11075 2005

[60] H Hara N Orita S Hatano et al ldquoEffect of tea polyphenols onfecal flora and fecal metabolic products of pigsrdquo The Journal ofVeterinary Medical Science vol 57 no 1 pp 45ndash49 1995

[61] N Ishihara D-C Chu S Akachi and L R Juneja ldquoImprove-ment of intestinal microflora balance and prevention of diges-tive and respiratory organ diseases in calves by green teaextractsrdquo Livestock Production Science vol 68 no 2-3 pp 217ndash229 2001

[62] P Dolara C Luceri C De Filippo et al ldquoRed wine polyphenolsinfluence carcinogenesis intestinal microflora oxidative dam-age and gene expression profiles of colonicmucosa in F344 ratsrdquoMutation Research-Fundamental and Molecular Mechanisms ofMutagenesis vol 591 no 1-2 pp 237ndash246 2005

[63] S Sembries G Dongowski K Mehrlander F Will and HDietrich ldquoPhysiological effects of extraction juices from applegrape and red beet pomaces in ratsrdquo Journal of Agricultural andFood Chemistry vol 54 no 26 pp 10269ndash10280 2006

[64] S Sembries G Dongowski G Jacobasch K Mehrlander FWill andH Dietrich ldquoEffects of dietary fibre-rich juice colloidsfrom apple pomace extraction juices on intestinal fermentationproducts and microbiota in ratsrdquo British Journal of Nutritionvol 90 no 3 pp 607ndash615 2003

[65] A Viveros S Chamorro M Pizarro I Arija C Centeno andA Brenes ldquoEffects of dietary polyphenol-rich grape productson intestinal microflora and gut morphology in broiler chicksrdquoPoultry Science vol 90 no 3 pp 566ndash578 2011

[66] A H Smith and R I Mackie ldquoEffect of condensed tannins onbacterial diversity andmetabolic activity in the rat gastrointesti-nal tractrdquo Applied and Environmental Microbiology vol 70 no2 pp 1104ndash1115 2004

[67] M Massot-Cladera T Perez-Berezo A Franch M Castelland F J Perez-Cano ldquoCocoa modulatory effect on rat faecalmicrobiota and colonic crosstalkrdquo Archives of Biochemistry andBiophysics vol 527 no 2 pp 105ndash112 2012

[68] M Larrosa M J Yanez-Gascon M V Selma et al ldquoEffectof a low dose of dietary resveratrol on colon microbiotainflammation and tissue damage in a DSS-induced colitis ratmodelrdquo Journal of Agricultural and Food Chemistry vol 57 no6 pp 2211ndash2220 2009

[69] A-L Molan Z Liu andM Kruger ldquoThe ability of blackcurrantextracts to positively modulate key markers of gastrointestinalfunction in ratsrdquoWorld Journal ofMicrobiologyampBiotechnologyvol 26 no 10 pp 1735ndash1743 2010

[70] A Lacombe R W Li D Klimis-Zacas et al ldquoLowbush wildblueberries have the potential to modify gut microbiota andxenobiotic metabolism in the rat colonrdquo PLoS ONE vol 8 no6 Article ID e67497 2013

[71] R Saad M R Rizkallah and R K Aziz ldquoGut Pharmacomicro-biomics the tip of an iceberg of complex interactions betweendrugs and gut-associated microbesrdquo Gut Pathogens vol 4 no1 article 16 2012

[72] E J J Van Velzen J A Westerhuis J P M van Duynhovenet al ldquoMultilevel data analysis of a crossover designed humannutritional intervention studyrdquo Journal of Proteome Researchvol 7 no 10 pp 4483ndash4491 2008

[73] T Okubo N Ishihara H Takahashi et al ldquoEffects of partiallyhydrolyzed guar gum intake on human intestinal microfloraand itsmetabolismrdquoBioscience Biotechnology andBiochemistryvol 58 no 8 pp 1364ndash1369 1994

[74] V Mai H A Katki H Harmsen et al ldquoEffects of a controlleddiet and black tea drinking on the fecalmicroflora compositionand the fecal bile acid profile of human volunteers in a double-blinded ramdomized feeding studyrdquo The Journal of Nutritionvol 134 no 2 pp 473ndash478 2004

[75] J-S Jin M Touyama T Hisada and Y Benno ldquoEffectsof green tea consumption on human fecal microbiota withspecial reference to Bifidobacterium speciesrdquoMicrobiology andImmunology vol 56 no 11 pp 729ndash739 2012

[76] J Yamakoshi S Tokutake M Kikuchi Y Kubota H Konishiand T Mitsuoka ldquoEffect of proantocyanidin -rich extract fromgrape seed on human fecal flora and fecalodorrdquo FASEB Journalvol 15 no 4 p A633 2001

[77] X Tzounis A Rodriguez-Mateos J Vulevic G R Gibson CKwik-Uribe and J P E Spencer ldquoPrebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomizedcontrolled double-blind crossover intervention studyrdquo TheAmerican Journal of Clinical Nutrition vol 93 no 1 pp 62ndash722011

[78] M I Queipo-Ortuno M Boto-Ordonez M Murri et alldquoInfluence of red wine polyphenols and ethanol on the gutmicrobiota ecology and biochemical biomarkersrdquo AmericanJournal of Clinical Nutrition vol 95 no 6 pp 1323ndash1334 2012

[79] K Shinohara Y Ohashi K Kawasumi A Terada and TFujisawa ldquoEffect of apple intake on fecal microbiota andmetabolites in humansrdquo Anaerobe vol 16 no 5 pp 510ndash5152010

[80] C I R Gill G J Mcdougall S Glidewell et al ldquoProfiling ofphenols in human fecal water after raspberry supplementationrdquoJournal of Agricultural and Food Chemistry vol 58 no 19 pp10389ndash10395 2010

[81] S Vendrame S Guglielmetti P Riso S Arioli D Klimis-Zacasand M Porrini ldquoSix-week consumption of a wild blueberry

BioMed Research International 15

powder drink increases Bifidobacteria in the human gutrdquoJournal of Agricultural and Food Chemistry vol 59 no 24 pp12815ndash12820 2011

[82] S Guglielmetti D Fracassetti V Taverniti et al ldquoDifferentialmodulation of human intestinal Bifidobacterium populationsafter consumption of a wild blueberry (Vaccinium angusti-folium) drinkrdquo Journal of Agricultural and Food Chemistry vol61 no 34 pp 8134ndash8140 2013

[83] T Clavel M Fallani P Lepage et al ldquoIsoflavones and func-tional foods alter the dominant intestinal microbiota in post-menopausal womenrdquo Journal of Nutrition vol 135 no 12 pp2786ndash2792 2005

[84] A Costabile A Klinder F Fava et al ldquoWhole-grain wheatbreakfast cereal has a prebiotic effect on the human gut micro-biota a double-blind placebo-controlled crossover studyrdquoBritish Journal of Nutrition vol 99 no 1 pp 110ndash120 2008

[85] A L Carvalho-Wells K Helmolz C Nodet et al ldquoDetermina-tion of the in vivo prebiotic potential of a maize-based wholegrain breakfast cereal a human feeding studyrdquo British Journalof Nutrition vol 104 no 9 pp 1353ndash1356 2010

[86] A Cuervo L Valdes N Salazar et al ldquoPilot study of diet andmicrobiota interactive associations of fibers and polyphenolswith human intestinal bacteriardquo Journal of Agricultural andFood Chemistry vol 62 no 23 pp 5330ndash5336 2014

[87] M Jaquet I Rochat J Moulin C Cavin and R BibilonildquoImpact of coffee consumption on the gut microbiota a humanvolunteer studyrdquo International Journal of FoodMicrobiology vol130 no 2 pp 117ndash121 2009

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Page 2: Review Article A Survey of Modulation of Gut Microbiota by ...downloads.hindawi.com/journals/bmri/2015/850902.pdf · Review Article A Survey of Modulation of Gut Microbiota by Dietary

2 BioMed Research International

Flavonols

O

OH

O

Isoflavones

O

O

Dihydroflavonols

O

OH

O

Flavanones

O

O

Chalcones

O

Flavones

O

O

O

OH

Flavan-3-ols

Anthocyanidins

OH

O+

Figure 1 Common phenolic compounds in food

of epidemiological studies have shown that the intake ofdiets rich in fruits and vegetables is inversely associated withthe risk of various chronic diseases such as coronary heartdisease specific cancers and neurodegenerative disorders[5ndash7] Indeed a range of pharmacological effects have beendemonstrated for different phenolic compoundsmdashespeciallyflavonoidsmdashthrough in vitro ex vivo and animal assays [8 9]However health effects of these compounds depend on theirbioavailability and therefore it is important to understandhow they are absorbed metabolized and eliminated from thebody in order to ascertain their in vivo actions

Modulation of gut microbiota by polyphenols has beena topic of increasing attention by the scientific communityin the last years Several studies have been carried out bydifferent authors ranging from the simplest experimentalapproaches on the effect of polyphenols on the growthof isolated intestinal bacteria to complex approximationsimplying the whole fecal microbiota either in fermentationexperiments (batch cultures and continuous simulators) orthrough compositional analysis of animal and human fecalsamplesThe existing knowledge about relationships betweenpolyphenols and gut microbiota has been object of manyreviews from different perspectives Thus some authorshave put their attention on the impact of food constituents(polyphenols included) in the gut microbiome [10 11] whileothers have focused on the effects of dietary polyphenolson microbial modulation and their potential implicationsin human health [12ndash15] Selma et al [16] wrote probablythe first review trying to put together the concepts of

microbial degradation of polyphenols and modulation ofgut microbiota by polyphenols and phenolic metabolitesThis two-way interaction between phenolics and intestinalbacteria has been also reviewed focusing on wine [17] andtea polyphenols [18] The development of improved biologyand microbial techniques has allowed notable advances inthe knowledge of the gut microbiota and their modulationby dietary components and hence polyphenolsThe potentialof the novel metabolomic approaches in the study of theimpact of polyphenols on gut microbiome has been recentlyreviewed [19]

Being aware of all this previous reviewing work we haveaimed to update the available information about modulationof gut microbiota by dietary polyphenols with a perspectivebased on the experimental approaches used After two gen-eral sections covering relevant aspects about gut microbiota(Section 2) and dietary polyphenols (Section 3) studies arepresented according to their experimental design batchculture fermentations (Section 4) gastrointestinal simulators(Section 5) animal model studies (Section 6) and humanintervention studies (Section 7) Main findings and generalconclusions generated from the different types of studies arefinally discussed (Section 8)

2 Gut Microbiota Composition and Analysis

The human gut is the natural habitat of a large diverse pop-ulation and dynamics of microorganisms mainly anaerobicbacteria which have adapted to life on mucosal surfaces

BioMed Research International 3

in the gut lumen The acquisition of gut microbiota beginsat birth and is strongly influenced by a range of factorsthat include host genetics immunological factors antibioticusage and also dietary habits [20] The microbial content ofthe gastrointestinal tract changes along its length rangingfrom a narrow diversity and low numbers of microbes inthe stomach to a wide diversity and high numbers in thelarge intestine which can reach 1012 CFUmL [21] Most ofintestinal bacteria belong to phylum Firmicutes (includingClostridium Enterococcus Lactobacillus and Ruminococcusgenera) and Bacteroidetes (including Prevotella and Bac-teroides genera) which constitute over 90 of known phy-logenetic categories and dominate the distal gut microbiota[22] Recently a novel classification of microbiota into threepredominant ldquoenterotypesrdquo dominated by three differentgenera Bacteroides Prevotella and Ruminococcus has beensuggested [23] In this line Wu et al [24] demonstratedthat long-term diet high in animal proteins and fats versussimple carbohydrates clustered the human subjects into thepreviously described enterotypes Bacteroides and PrevotellaHowever there is a current debate if the enterotypes shouldbe seen discontinuous or as a gradient [25] But in any casea common observation is that homeostasis and resilience arecoupled to a highly diverse gut microbiota in healthy peoplewhereas inflammatory and metabolic disorders are linked toperturbations in the composition andor functions of the gutmicrobiota [26]

Culture-based techniques employed to bacteria identifi-cation are fairly cheap laborious and time-consuming andgives a limited view of the diversity and dynamics of thegastrointestinal microbiota with less than 30 of gut micro-biotamembers having been cultured to date [27] Since 1990sthe introduction of novel molecular biological procedureshas made it possible to overcome some of these limitationswith the use of culture-independent methods [28] Theseprocedures are based on sequence divergences of the smallsubunit ribosomal RNA (16S rRNA) and include techniquessuch as denaturing gradient gel electrophoresis (DGGE)terminal restriction fragment length polymorphism (T-RFLP) fluorescence in situ hybridization (FISH) quantitativepolymerase chain reaction (qPCR) DNA microarrays andnext-generation sequencing (NGS) of the 16S rRNA geneor its amplicons [29] NGS techniques have promoted theemergence of new high-throughput technologies such asgenomics metagenomics transcriptomics and metatran-scriptomics Metagenomics gives a more in-depth unbiasedmicrobial analysis beyond the group level and involvesmultiple species besides showing shorter sequencing speedextended read length and lower costs [30] However theenormous amount of data generated becomes cumbersome toanalyze and requires lots of dedicated time as well as expertiseto manage [29]

In the context of polyphenol-microbiota interactions theemerging high-throughput meta-genomic transcriptomicand proteomic approaches can be adopted to identify genesand micro-organisms involved in polyphenol (in)activationand conversion to reconstruct metabolic pathways and tomonitor how microbial communities adjust their metabolic

activities upon polyphenol exposure [30] Application ofthese technologies to human fecal samples requires fur-ther investigation to determine how these samples reflectmetabolism inside the gut and ultimately to improve theunderstanding of the impact of polyphenols on host health[12 31]

3 Dietary Polyphenols

It has been estimated that 90ndash95 of dietary polyphenols arenot absorbed in the small intestine and therefore reach thecolon [32] although absorption and metabolism are largelyinfluenced by their chemical structure Most flavonoids arepoorly absorbed from the small intestine and are highlymetabolized in the large intestine Isoflavones seem to bethe best absorbed dietary flavonoids catechins flavanonesand flavonol glycosides are intermediate whereas proantho-cyanidins flavan-3-ol gallates and anthocyanins would bethe worst absorbed [33]

The first step in the metabolism of flavonoids with theexception of flavan-3-ols (ie catechins and proanthocyani-dins) is likely to be deglycosylation before absorption inthe small intestine Hydrolysis of some flavonoid glycosidemight already occur in the oral cavity as both saliva andoral microbiota show 120573-glucosidase activity But the mech-anism most usually assumed for flavonoid deglycosylation ishydrolysis by lactase phlorizin hydrolase (LPH) in the brush-border of the small intestine epithelial cells [34 35] so thatthe resulting aglycones would enter the enterocyte by passivediffusion The resulting aglycone is rapidly biotransformedby phase II enzymes within the enterocyte and further inthe liver so that conjugated metabolites (ie glucuronidesO-mehtylethers andor sulphates) through the respectiveaction of UDP-glucuronosyltransferase (UGT) catechol-O-methyltransferase (COMT) and sulphotransferases would bethe circulating forms in the human body [36 37]

Generally a relevant fraction of dietary flavonoids isnot absorbed in the small intestine and together withthe conjugated metabolites that returned to the intestinallumen via enterohepatic circulation reaches the large intes-tine where compounds are subjected to the action of thecolonic microbiota Intestinal bacteria show diverse degly-cosylating activities thus releasing aglycones that might beabsorbed in a lesser extent and more probably degradedto simpler phenolic derivatives [38 39] Degradation offlavonoid aglycones by colonic microbiota involves ring-C cleavage and reactions affecting functional groups suchas dehydroxylation demethylation or decarboxylation [39]Various hydroxylated aromatic compounds derived from theA-ring (eg phloroglucinol 34-dihydroxybenzaldehyde or34-dihydroxytoluene) and phenolic acids derived from theB-ring have been reported as relevant products of the colonictransformation of flavonoids [40] It has become evidentthat the beneficial effects attributed to dietary polyphenolsappear to be due more to phenolic metabolites formed in thegastrointestinal tract mainly derived from the action of gutbacteria rather than to the original forms found in food [41]

In subsequent sections main findings related to themodulation of gut microbiota by polyphenols are presented

4 BioMed Research International

as obtained from different methodological approaches andmicrobial analysis techniques

4 Studies Using Batch Culture Fermentations

Although in vivo human or animal intervention trials arephysiologically most relevant to study both polyphenolmetabolism and microbial modulation in vitro tools havebeen designed to simulate intestinal conditions In combi-nation with in vivo trials in vitro experiments may help toelucidate the extent bioconversion processes mediated by thehost itself [42 43] The complexity of in vitro gut models isdiverse ranging from simple static models (batch culture fer-mentation) to advanced continuous models (gastrointestinalsimulators)

Simple static gut models also known as batch-typecultures are generally closed systems using sealed bottlesor reactors containing suspensions of fecal material that aremaintained under anaerobic conditions They are relativelyeasy to operate and cost-effective have a fair throughputand allow for parallel screening This model approach isprimarily used to assess the stability of polyphenols in thepresence of human-derived gut microbiota and to evaluatewhich environmental conditions favor or limit polyphenolbioconversion However these static gut models are onlyadequate for simulating short-term conditions in the gutfor assessment of long-term adaptations of the gut microbialcommunity more complex dynamic models are needed[12]

Table 1 reports different studies of modulation of gutmicrobiota by dietary polyphenols using batch-type culturesDetails about fermentation conditions (fecal concentrationpolyphenol origin and dose and incubation time) andmicro-bial techniques used and main effects on bacteria groups(growth enhancement growth inhibition or no effect) havebeen included As general characteristics fecal fermentationsemployed feces concentration le10 (wv) and lasted 48 hmaximum Both pure phenolic compounds and phenolic-rich extracts were added to the fecal medium at a finalconcentration lt10 (wv) and changes in specific bacterialgroups weremainly assessed by FISH analysis A first relevantexperiment using batch culture fermentation was carriedout by Tzounis et al [44] who found that the flavan-3-olmonomers [(minus)-epicatechin and (+)-catechin] promoted thegrowth of Clostridium coccoides-Eubacterium rectale groupwhich is known to produce large amounts of butyrate a short-chain fatty acid (SCFA) with anti-inflammatory and anti-neoplasic properties (+)-catechin also increased the growthof Lactobacillus-Enterococcus spp Bifidobacterium spp andEscherichia coli but decreased the growth of Clostridiumhistolyticum Also using standard compounds Hidalgo et al[45] found that anthocyanins (ie malvidin-3-glucoside andamixture of anthocyanins) significantly enhanced the growthof Lactobacillus-Enterococcus spp and Bifidobacterium sppIn addition malvidin-3-glucoside showed a tendency topromote the growth of the C coccoides-E rectale group

Similar results have been observed in batch culturefermentations with phenolic-rich extracts from different

sourcesMolan et al [46] found that the addition of blueberryextracts to a mixture of fecal bacterial populations signifi-cantly increased the number of lactobacilli and bifidobacteria(Table 1) In the same line Bialonska et al [47] reportedenhancement of the growth of total bacteria Bifidobacteriumspp and Lactobacillus-Enterococcus spp in response to acommercial extract of pomegranate without influencing theC coccoides-E rectale and C histolyticum groups (Table 1)Mandalari et al [48] suggested a potential prebiotic effectfor natural and blanched almond skins as these foodstuffs infermentations with fecal microbiota significantly increasedthe populations of bifidobacteria and C coccoides-E rectalegroup and decreased the number of C hystolyticum groupThese authors related the possible prebiotic effect by almondskins not only to a high amount of dietary fibre but also tosome phenolic compounds such as ferulic acid flavan-3-olsand flavonols present in the almond skins [48] Fogliano et al[49] carried out an in vitro fermentation with a water-insoluble cocoa fraction in a three-stage continuous culturecolonicmodel system It was observed that this cocoa fractionpresented prebiotic activity producing a significant increasein lactobacilli and bifidobacteria as well as an increase inbutyrate production They concluded that the coexistenceof fermentable polysaccharides and free flavanol monomersin cocoa such as catechins might be very effective in themodification of gut microbiota Similar conclusions weredrawn by Pozuelo et al [50] who found a significant increaseof the growth of Lactobacillus reuteri and Lactobacillusacidophilus in the presence of a grape antioxidant dietary fibernaturally obtained from red grapes Our research group car-ried out several batch culture fermentations of two flavan-3-ol fractions with different degree of polymerisation and winepolyphenols with fecal microbiota from different healthyvolunteers [51 52] Both flavan-3-ol fractions promoted thegrowth ofLactobacillusEnterococcus spp and inhibited theChistolyticum group during fermentation although the effectswere only statistically significant with the less polymerizedfractionWine polyphenols only showed a slight inhibition intheC histolyticum group probably due to their lower contentin flavan-3-ols

Additionally this type of fermentations has also beenused to assess the contribution of certain probiotic strainsto the colonic metabolism of polyphenols In this senseBarroso et al [53] carried out fermentations of a red wineextract inoculated with human microbiota obtained fromthe colonic compartments of a dynamic simulator in thepresence and absence of the probiotic strain L plantarumIFPL935 Microbial analysis by qPCR indicated that redwine polyphenols induced greater variations among in vitrobatches harboring different colon-region (ascending colondescending colon and effluent) microbiota than those foundwhen L plantarum IFPL935 was added Batches inoculatedwith microbiota from the ascending colon were shown toharbor the major proportion of saccharolytic bacteria (Bac-teroides Bifidobacterium and Prevotella) whereas Clostrid-ium groups were found in major numbers in the batchesinoculated with microbiota simulating the distal regions [53](Table 1)

BioMed Research International 5

Table1Stud

iesu

singbatchcultu

referm

entatio

n

Reference

Fecal

concentration

Phenolic

compo

undfood

Dose

Timeo

fincubatio

nMicrobial

techniqu

eGrowth

enhancem

ent

Growth

inhibitio

nNoeffect

Tzou

nise

tal

(2008)

[44]

10w

v(+)-catechin

150m

gL

1000

mgL

lt48

hFISH

Lactobacillus-

Enterococcus

spp

Bifid

obacteriu

mspp

Ccoccoides-E

rectale

grou

pE

coli

Chisto

lyticum

grou

p

Molan

etal(2009)

[46]

01

vv

Blueberryextracts

510

and25

48h

FISH

Lactob

acilli

Bifid

obacteria

Bialon

skae

tal

(2010)

[47]

10w

vPo

megranate

extractand

punicalagin

10

48h

FISH

Totalbacteria

Bifid

obacteriu

mspp

Lactobacillus-

Enterococcus

spp

Ccoccoides-E

rectale

grou

pC

histo

lyticum

grou

p

Mandalarietal

(2010)

[48]

10w

vAlm

ondskins

1w

vpredigested

almon

dskins

lt24

hFISH

Bifid

obacteria

Ccoccoides-E

rectale

grou

p

Chisto

lyticum

grou

p

Fogliano

etal

(2011)[49]

5w

vWater-in

soluble

cocoafraction

1w

v36

hFISH

Bifid

obacteria

Lactob

acilli

Cuevae

tal(2013)

[51]

10w

vGrape

seed

extract

fractio

ns300ndash

450m

gL

lt48

hFISH

Lactobacillus-

Enterococcus

spp

Chisto

lyticum

grou

p

Hidalgo

etal

(2012)

[45]

10w

v

Malvidin-3-O-

glucoside

Antho

cyanidins

mixture

20mgLand

200m

gL

4850

mgLand

48500m

gL

lt24

hFISH

Lactobacillus-

Enterococcus

spp

Bifid

obacteriu

mspp

Ccoccoides-E

rectale

grou

p

Sanchez-Patanet

al(2012)[52]

1wv

Redwinee

xtract

600m

gL

48h

FISH

Chisto

lyticum

grou

p

Lactobacillus-

Enterococcus

spp

Barrosoetal

(2013)

[53]

Redwinee

xtract

500m

gL

48h

qPCR

Lactobacillus

spp

Bifid

obacteriu

mspp

Bacteroidesspp

Ru

minococcusspp

6 BioMed Research International

Table 2 Studies using the gastrointestinal simulators (ie SHIME)

Reference Simulator Phenoliccompoundfood Dose Time Microbial

techniquePopulationincrease Population decrease

De Boeveret al (2000)[57]

SHIME Soy germ powder 25 gday 2 weeks Plate count

EnterobacteriaceaeColiforms

Lactobacillus sppStaphylococcus sppClostridium spp

Kempermanet al (2013)[31]

Twin-SHIME Black tea extract

3 times dailydosing(1000mg

polyphenolsas total daily

dose)

2 weeks

Plate countqPCR

PCR-DGGEpyrosequencing

Klebsiella sppEnterococci

Akkermansia spp

BifidobacteriaBlautia coccoidesAnaeroglobus sppVictivallis spp

Kempermanet al (2013)[31]

Twin-SHIME

Red wine-grapeextract

3 times dailydosing(1000mg

polyphenolsas total daily

dose)

2 weeks

Plate countqPCR

PCR-DGGEpyrosequencing

Klebsiella sppAlistipes spp

Cloacibacillus sppVictivallis spp

Akkermansia spp

BifidobacteriaBlautia coccoides

groupAnaeroglobus spp

Subdoligranulum sppBacteroides

5 Studies Using HumanGastrointestinal Simulators

In contrast to short-duration experiments with static gutmodels longer-term experiments are required when theadaptation of the gut microbial community to dietarypolyphenols needs to be assessed To this end dynamic invitro gut models such as the ldquoReadingrdquo model [54] theSimulator of the Human Intestinal Microbial Ecosystem(SHIME) the TNO Intestinal Model 2 (TIM2) [55 56] andthe recent gastrointestinal simulator set up in our Institute(SIMGI) (unpublished work) have been developed where gutmicrobiota are cultured over a longer time frame (days toweeks) in one or multiple connected pH controlled vesselsrepresenting different parts of the gastrointestinal tract

As an example of the versatility and potential of humangastrointestinal simulators Table 2 reports a series of studiesabout modulation of gut microbiota by polyphenols usingthe SHIME [57 58]This validatedmodel comprises stomachand small intestinal sections for predigestion of food aswell as vessels stimulating the ascending transcending anddescending parts of the human colon allowing assessment ofchanges in the different colonic areas that are very challengingto access in a human intervention However it should beunderlined that this approach takes for granted that theextracts reach intact the colonic region and no nutrientabsorption is consideredThe use of the SHIME to investigatethe effects of a soy germ powder on the fermentative capacityof the simulated microbiota of the colon was the aim of astudy carried out by De Boever et al [57]They observed thatthe addition of the soy germ powder in a 2-week treatmentresulted into an overall increase of bacterial marker pop-ulations (Enterobacteriaceae coliforms Lactobacillus sppStaphylococcus spp and Clostridium spp) with a significantincrease of 2 log10 units in the Lactobacillus spp populationMore recently Kemperman et al [31] using the twin-SHIME

model studied the influence of a bolus dose and a 2-weekcontinuous administration of complex dietary polyphenolsfrom black tea or red wine grape extracts on the colonicmicrobiota The Twin-SHIME system involving two modelsthat run in parallel was inoculatedwith the same fecal samplefor direct comparison of the effect of the two polyphenoltypes A combination of analyses including cultivation PCR-denaturing gradient gel electrophoresis (DGGE) quantita-tive PCR and high throughput pyrosequencing of the 16Sribosomal RNA gene was applied to characterize micro-bial community changes This study showed that complexpolyphenols in the context of a model system can modulateselect members of the human gut microbiota revealing noveltargets potentially involved in polyphenolmetabolism andorresistant microbes to be further investigated for polyphenolmetabolism or resistance mechanisms [31]

6 Animal Models Studies

It is widely assumed that preliminary evidence should bewarranted in animal models before human interventiontrials Animal models contribute to better understanding themechanisms and biological effects that could be likely tohappen in the human body The metabolism of polyphenolshas been object of numerous animal studies (mostly inrodents) especially for their impact on metabolic disorders[58] but only a few of these studies have followed thedynamics and composition of the intestinal microbiota inassociation with polyphenol metabolites retrieved from thehost Caution is required in extrapolating results to humansbecause culture-independent comparisons have revealed thatmost bacterial genera and species found in mice are not seenin humans although the distal gut microbiota of mice andhumans harbors the same bacterial phyla [59] In this sectionstudies performed in animals in order to assess the effects ofpolyphenols on the modulation of intestinal microbiota are

BioMed Research International 7

Table 3 Animal model studies

Reference Animal Phenoliccompoundfood Dose Treatment

durationMicrobialtechnique Population increase Population decrease

Hara et al(1995) [60] Pigs Tea polyphenols 02 (free access) 2 weeks Plate count Lactobacilli

Total bacteriaBacteroidaceaeC perfringens

Ishihara et al(2001) [61] Calves Green tea extracts 15 gday 4 weeks Plate count

Bifidobacterium sppLactobacillus sppC perfringens

Smith andMackie (2004)[66]

Rats

Proantocyanidinsextracted from

Acaciaangustissima

07 (low tannindiet) and 20

(high tannin diet)

35 weekstreatment +35 weekswashout

PCR-DGGEDot blot

hybridization

Bacteroides fragilisgroup

Bacteroides-Prevotella-

Porphyromonas group

Enterobacteriaceae

C leptum group

Dolara et al(2005) [62] Rats

Red winepolyphenolspowder

50mgkg 16 weeks Plate count LactobacilliBifidobacteria

PropionibacteriaBacteroidesClostridia

Sembries et al(2006) [63] Rats Apple juice free access 4 weeks Plate count Lactobacilli

BifidobacteriaSembries et al(2003) [64] Rats Apple pomace

juice colloid5 suppl diet(free access) 6 weeks Plate count

FISH Bacteroidaceae

Larrosa et al(2009) [68] Rats Resveratrol 1mgkgday 25 days Plate count Lactobacilli

Bifidobacteria

Molan et al(2010) [69] Rats

Blackcurrantextracts (leaf or

berry)

3 timesweek(i) 30mgkg

(leaf)(ii) 134mgkg

(berry)

4 weeks FISH

Lactobacilli (berryextract)

Bifidobacteria (leafand berry extracts)

Viveros et al(2011) [65]

Broilerchicks

Grape pomaceconcentrate(GPC) Grapeseed extract

(GSE)

60 gkg diet(GPC)

72 gkg diet(GSE)

(free access)

21 days Plate countT-RFLP

E coliEnterococcus sppLactobacillus spp

Lacombe et al(2013) [70] Rats Lowbush wild

blueberries

20 g feedday(eq 24 plusmn 52mganthocyaninday)

6 weeks Metagenomicsequencing

Thermonospora sppCorynebacteria spp

Slackia spp

Lactobacillus sppEnterococcus spp

summarized (Table 3) Experiments were mainly performedin rats although other larger animals such as chicks calvesor pigs have also been used Gut microbial communities wereevaluated by diverse methodologies including culture-basedmethods (plate count) DGGE FISH T-RFLP qPCR andmetagenomic sequencing

Animal studies performed in pigs [60] and in calves[61] demonstrated that tea polyphenols administration con-tributed to the improvement in the composition of the intesti-nal microbiota Thus the administration of tea polyphenolsin pigs significantly increased the levels of lactobacilli whilstit diminished the levels of total bacteria and Bacteroidaceaeand a tendency to decrease in lecithinase positive clostridiaincludingC perfringenswas also observed [60] However thereduction rate of Bifidobacterium spp and Lactobacillus sppwas slowwhile that ofC perfringensdecreased faster in calvessupplemented with the green tea extract [61]

Dolara et al [62] showed that treatment with winepolyphenols in carcinogen-treated F344 rats was associated

with a strong variation in the colonic microbiota comparedto the control-fed rats Although the total bacterial counts andanaerobeaerobe ratio of microorganisms in the feces frompolyphenol-treated rats were similar to that from control ratspropionibacteria Bacteroides and Clostridia decreased whilelactobacilli and bifidobacteria increased Based on additionalexperiments these authors concluded that reduction ofoxidative damage modulation of colonic flora and variationin gene expression may be all connected in the action of winepolyphenols on the intestinal function and carcinogenesis

In other study rats fedwith apple juice instead of drinkingwater showed more lactobacilli and bifidobacteria in freshfeces that differed from the controls by one-log10 colonyforming units [63] The same research group studied theeffect of colloids isolated from apple pomace extraction juiceson the intestinal microbiota in Wistar rats An increaseof Bacteroidaceae in almost one-log10 higher counts wasobserved in feces of rats fed with apple juice colloid thancontrol rats [64] Another animal experiment conducted to

8 BioMed Research International

study the effect on intestinal microbiota of the inclusionof grape pomace extracts in the diet of broiler chicks [65]found that for the cecum birds fed grape extracts had higherpopulations of E coli Lactobacillus and Enterococcus speciesthan birds in any other treatment group These authorsconcluded that grape polyphenol-rich products modified thegut morphology and intestinal microbiota and increased thebiodiversity degree of intestinal bacteria in broiler chicks

Inclusion of condensed tannins (proanthocyanidins)extracted from Acacia angustissima on rat diet resulted ina shift in the predominant bacteria towards tannin-resistantGram-negative Enterobacteriaceaeand Bacteroides speciesand reduced the number of Gram-positive C leptum group[66] Compatible results were obtained in an experimentwith rats fed a proanthocyanidin-rich cocoa preparation [67]where the authors found a significant decrease in the propor-tion of Bacteroides Clostridium and Staphylococcus generain the feces of cocoa-fed animals Interestingly reductions inClostridium species were found to correlate with weight lossand decrease in body mass index

Larrosa et al [68] observed an increase in lactobacilliand bifidobacteria when resveratrol (3541015840-trihydroxy-trans-stilbene) which naturally occurs in grapes and grape-derivedfoodstuffs such as red wine was administered to rats Afterinduction of colitis by dextran sulphate sodium proliferationof both E coli and enterobacteria was lower in rats treatedwith resveratrol than in control rats This could be the resultof an indirect effect of resveratrol-supplemented diet whichincreased bifidobacteria and lactobacilli counts preventingthe colonization and invasion of tissues by enterobacteriaincluding E coli

Prebiotic activity of wild blackcurrant extracts observedin in vitro experiments was further confirmed in rats byMolan et al [69] A significant increase in the populationsize of lactobacilli and bifidobacteria was observed after dailyadministration of those extracts to rats Similarly a grapeantioxidant dietary fibre preparation was found to increasethe population of Lactobacillus spp when fed to rats whereaspopulations of Bifidobacterium spp decreased and changes inE coli and Bacteroides vulgatus counts were not significant[50]

Recently Lacombe et al [70] studied the composition andfunctional potential of the colon microbiota from rats feda diet enriched in lowbush wild blueberries Application ofnovel metagenomic techniques (Illumina shotgun sequenc-ing) revealed a significant reduction in the relative abundanceof the genera Lactobacillus and Enterococcus associated withwild blueberries intake In addition hierarchical analysisshowed a significant increase in the relative abundanceof the phylum Actinobacteria the order Actinomycetalesand several novel genera under the family Bifidobacteri-aceae and Coriobacteriaceae in the blueberries group Theauthors indicated that although the microbiome of ratsdiffers from humans the applied model was a powerfultool to study population dynamics and related metabolicfunctions Metagenomic studies can determine microbialcommunity profiles gene presenceabsence and abundanceand functional repertoire however they can only infer an

observed phenotype since a gene presence does not imply itsexpression or functionality [71]

7 Human Intervention Studies

Investigations involving the use of humans potentially pro-vide the best models for studying the interactions of foodcomponents (eg polyphenols) with microbiota although invivo intervention trials hold inevitable practical and ethicallimitations [12] The use of cross-over designs where volun-teers serve as their own control permits multilevel analysisschemes that increase power but requires a relevant numberof volunteers to allow for statistically significant multivariatemodels [72] Up to now only a few studies have examinedthe in vivo impact of dietary polyphenols on the humangut microbiota and most of them were focused on singlepolyphenol molecules and selected bacterial populations Asummary of human intervention studies about effects ofpolyphenols in the modulation of the intestinal microbiotais collected in Table 4 In these studies the polyphenol doseused was much dependent on the type of food preparationand its concentration normally ranging from 01 to 4 thetreatment time was also variable from 10 days to 2 monthsand the applied microbial techniques were diverse (platecount DGGE FISH T-RFLP and qPCR)

In a study with a reduced number of subjects (119899 =8) Okubo et al [73] reported a notably increase in thepercentages of Bifidobacterium spp in total fecal countsafter an intervention with a product containing 70 of teapolyphenols A significant decrease of C perfringens andother Clostridium spp was also observed during the intakeperiod However in a crossover feeding study (number ofvolunteers not reported) that investigated the effects of blacktea drinking on hypercholesterolemic volunteers Mai et al[74] found that although specific bacterial groups were notaffected the total amount of bacteria significantly decreasedhighlighting large interindividual variations More recentlyan intervention study (119899 = 10) by Jin et al [75] confirmedan overall tendency for the proportion of bifidobacteria toincrease because of green tea consumption even thoughthere were interindividual differences in the Bifidobacteriumspecies

Yamakoshi et al [76] showed that administration of aproanthocyanidin-rich extract from grape seeds to healthyvolunteers (119899 = 9) significantly increased the fecal number ofBifidobacterium whereas the number of putrefactive bacteriasuch as enterobacteria tended to decrease The interactionbetween proanthocyanidins and intestinal bacteria was alsoconfirmed in a randomized double-blind crossover andcontrolled intervention study (119899 = 22) ingesting two cocoadrinks exhibiting low and high polyphenol content [77]Compared with the consumption of the low-flavan-3-olcocoa drink the daily consumption of the high-flavan-3-ol cocoa drink significantly increased the bifidobacteria andlactobacilli populations but significantly decreased clostridiacounts

Queipo-Ortuno et al [78] performed a randomizedcrossover and controlled trial (119899 = 10) consisting of theintake of red wine dealcoholized red wine and gin over

BioMed Research International 9

Table4Hum

aninterventio

nstu

dies

Reference

Volunteer

number

Phenolic

compo

undfood

Dose

Treatm

ent

duratio

nMicrobial

techniqu

ePo

pulatio

nincrease

Popu

latio

ndecrease

Noeffect

Oku

boetal

(1994)[73]

8Green

tea

(Sun

phenon

)04g

3tim

esper

day

4weeks

Platec

ount

Cperfr

ingens

Clostridium

spp

Yamakoshi

etal(2001)[76]

9Proantocyanidin-

richextractfrom

grapes

eeds

05g

day

6weeks

Platec

ount

Bifid

obacteriu

mspp

Enterobacteriaceae

Maietal

(200

4)[74]

15Blacktea

700m

gteas

olids5

times

perd

ay21

days

FISH

DGGE

Totalbacteria

Nochanges

Claveletal

(2005)

[83]

39Isofl

avon

es100m

gday

2mon

ths

TTGEFISH

Ccoccoides-E

rectale

grou

pBifid

obacteriu

mspp

Lactobacillus-

Enterococcus

spp

Faecalibacteriu

mprau

snitziisubgroup

Costabileetal

(2008)

[84]

31Who

legrainwheat

cereals

48gday

3weeks

FISH

Bifid

obacteria

Lactob

acilli

Totalbacteria

Bacteroidesspp

C

histo

lyticum

perfringens

grou

pAc

etobacteriu

mspp

Jaqu

etetal

(200

9)[87]

16Coff

ee3cupsday

3weeks

FISH

DGGE

Bifid

obacteriu

mspp

Carvalho

-Wellsetal

(2010)

[85]

32Who

legrainmaize

cereals

48gday

3weeks

FISH

Bifid

obacteria

Totalbacteria

Bacteroidesspp

C

histo

lyticum

perfringens

grou

pAc

etobacteriu

mspp

Gill

etal

(2010)

[80]

10Ra

spberrypu

ree

20gday

4days

PCR-DGGE

Nochangesinthep

rofileo

fcolonicb

acteria

Shinoh

arae

tal(2010)[79]

8Ap

ples

2applesday

2weeks

Platec

ount

Lactobacillus

spp

Streptococcusspp

En

terococcus

spp

Enterobacteriaceae

lecithinase-po

sitive

clostrid

iainclu

ding

Cperfr

ingens

Pseudomonas

spp

10 BioMed Research International

Table4Con

tinued

Reference

Volunteer

number

Phenolic

compo

undfood

Dose

Treatm

ent

duratio

nMicrobial

techniqu

ePo

pulatio

nincrease

Popu

latio

ndecrease

Noeffect

Tzou

nise

tal

(2011)[77]

22Cocoa

flavano

l494m

gday

29mgday

4weeks

FISH

Bifid

obacteriu

mspp

Lactobacillus

spp

Chisto

lyticum

perfringens

grou

p

Vend

ramee

tal(2011)[81]

15Wild

blueberry

drink

25gwild

blueberriesd

ay6weeks

qPCR

Bifid

obacteriu

mspp

Lacidophilus

Bacteroidesspp

Prevotellaspp

Enterococcus

spp

Ccoccoides

Queipo-

Ortun

oetal

(2012)

[78]

10Re

dwine

272m

Lday

20days

qPCR

Enterococcus

spp

Prevotellaspp

Bacteroides

Bifid

obacteriu

mspp

Bacteroidesu

niform

isEggerthella

lenta

Blautia

coccoides-E

rectaleg

roup

Clostridium

spp

Chisto

lyticum

group

Actin

obacteria

Jinetal(2012)

[75]

10Green

tea

1000

mLday

10days

T-RF

LPqP

CRBifid

obacteriu

mspp

Gug

lielm

ettiet

al(2013)[82]

15Wild

blueberries

drink

25gwild

blueberriesd

ay6weeks

qPCR

Blongum

subspinfantis

Cuervo

etal

(2014)

[86]

38

Dairy

prod

ucts

Fruits

Vegetables

Cereals

Food

intake

was

recorded

usingan

annu

alfood

frequ

ency

questio

nnaire

qPCR

Lactobacillus

Bcoccoides

Clep

tum

BioMed Research International 11

three consecutive periods After the red wine period thebacterial concentrations of proteobacteria fusobacteria Fir-micutes and Bacteroidetes markedly increased comparedwith the washout period significant increases in the num-ber of Bifidobacterium spp and Prevotella spp were alsoobserved However Lactobacillus spp Clostridium spp andC histolyticum group concentrations remained unchangedthroughout the study

In a small-scale observational study (119899 = 8) Shinoharaet al [79] found that the number of bifidobacteria in fecessignificantly increased during apple intake and the numbersof Lactobacillus spp Streptococcus spp and Enterococcusspp tended to increase On the contrary enterobacteriaand lecithinase-positive clostridia including C perfringensand Pseudomonas species tended to decrease Howeverthat study did not use culture-independent microbiologytechniques and suffered from the lack of a control groupAlso in relation to fruits another small human interventionstudy (119899 = 10) with raspberry puree [80] did not observestatistically significant alterations in the profile of colonicbacteria probably due to high interindividual variation infecal bacteria although the profiles of microbial metabolitesof raspberry polyphenols varied greatly between individualsindicating that the type of gut microbiota affects cataboliteprofiles released by bacteria in the colonThis lack of effect onthe intestinal microbiota after the intake of raspberry pureemight also be due to the short duration of the treatment aswell as the techniques employed to quantify the intestinalmicrobiota

Vendrame et al [81] studied the potential prebioticactivity of a drink elaborated fromwild blueberries especiallyrich in anthocyanins in a small intervention trial (119899 = 15) Asignificant increase in Bifidobacterium spp and L acidophilusgroup was detected while no significant differences wereobserved for Bacteroides spp Prevotella spp Enterococcusspp and C coccoides In a further paper of the same group[82] seven different intragenus bifidobacteria taxonomicclusters that were among the most common and abundantbifidobacteria species inhabiting the human gutwere targetedin the same samples It was found thatB adolescentisB breveB catenulatumpseudocatenulatum and B longum subsplongumwere always present in the group of subjects enrolledwhereas B bifidum and B longum subsp infantis were notIn spite of the large interindividual variability a significantincrease of B longum subsp infantis cell concentration wasobserved in the feces of volunteers after the wild blueberrydrink treatment which was attributed to the presence ofprebiotic (bifidogenic) molecules from blueberries possiblyfibers and glycosylated anthocyanins

In a study with postmenopausal women (119899 = 39)Clavel et al [83] found that isoflavone supplementationstimulated dominant microorganisms of the C coccoides-Erectale cluster Lactobacillus-Enterococcus group Faecalibac-terium prausnitzii subgroup and Bifidobacterium genus Itwas also suggested that the concentration of C coccoides-Erectale cluster was related to women capacity to excrete equolan intestinal metabolite from daidzein In two interventionstudies with whole grain breakfast cereals from wheat (119899 =31) and maize (119899 = 32) [84 85] the ingestion of both

products resulted in significant increases in fecal bifidobac-teria andor lactobacilli without changing the relative abun-dance of other dominant members of the gut microbiotaLittle or no changes were observed in the numbers of totalbacteria Bacteroides spp C histolyticumperfringens groupand Acetobacterium spp present in the feces However aswhole grains are good sources of dietary fiber it is difficult toascribe the observed effects only to the phenolic compoundspresent in these foods In this respect Cuervo et al [86] haverecently studied the correlations between the intake of fiberand polyphenols from diet and fecal microbiota compositionin a cohort of apparently healthy subjects Results showedthat the intake of soluble pectins and flavanones fromorangespresented a negative correlation with the levels of B coccoidesand C leptum By contrast the intake of white breadproviding hemicellulose and resistant starch was directlycorrelated with Lactobacillus

Finally another human trial (119899 = 16) carried out byJaquet et al [87] assessed the impact of a moderate con-sumption of instant coffee on the general composition ofthe human intestinal bacterial population Coffee bever-ages contain significant amounts of soluble fibre (mainlygalactomannans and arabinogalactan-proteins) and phenoliccompounds (chlorogenic acids) which arewell utilised by thehuman fecal microbiota It was observed that although fecalprofiles of the dominant microbiota were not significantlyaffected after the consumption of the coffee the populationof Bifidobacterium spp increased being the largest increaseobserved for those volunteers showing the lowest initialbifidobacteria levels

8 Conclusions

This review has tried to summarize the current knowledgein relation to the phenolic metabolism by gut microbiota andthemodulation of the gutmicrobiota by phenolic compoundsand polyphenol-rich dietary sourcesThere are evidences thatthe beneficial effects attribute to dietary polyphenols dependon their biotransformation by the gut microbiota Thereforeit is important to investigate the bacterial species impli-cated in the metabolism of dietary polyphenols and furtherresearch is still needed in relation to the resultant microbialmetabolites to ascertain their mechanisms of action Onthe other hand a great number of in vitro and in vivo (inanimals andhumans) studies showing the influence of dietarypolyphenols on gut-inhabiting bacteria have been publishedin recent years Although in vitro assays facilitate experimen-tation caution must be taken in extrapolating results to invivo situation as many factors are acting upon this processIn general in both in vitro and in vivo studies polyphenols orpolyphenol-rich sources have shown to influence the relativeabundance of different bacterial groups within the gut micro-biota reducing numbers of potential pathogens including Cperfringens and C histolyticum and certain Gram-negativeBacteroides spp and enhancing mainly beneficial Clostridiabifidobacteria and lactobacilli A better understanding of theinteraction between dietary polyphenols and gut microbiotathrough the emerging advances in high-throughput meta-genomic transcriptomic and proteomic approaches would

12 BioMed Research International

be essential in order to identify genes and micro-organismsinvolved in polyphenol (in)activation and conversion andthus to elucidate the implications of diet on the modulationof microbiota for delivering health benefits

Functional foods are considered to enhance the protectiveeffects against diseases derived from some food componentsIn the last decades dairy fermented foods have probablybeen one of the most-developed functional products andhave deserved intensive research In this expansion dairyfermented foods have been supplemented with fruits cerealsand other stuffs of plant origin all of which represent a highpercentage of the current market of the dairy industry Theseproducts have a healthy appeal which attracts consumersThus fruit juicesconcentrates and prepared fruits (in theform of pieces pulp and even flour) have been successfullyincorporated in dairy fermented foods as sources of prebioticfibers and phytochemicals Among these phytochemicalspresent in plant-derived foods polyphenols have gainedmuch interest due to their diverse potential beneficial effectsin human health The supplementation of dairy fermentedproducts with rich-polyphenolic stuffs (phenolic extractsphenolic-enriched fractions etc) seems to be an effectivetechnological option to improve the benefits of these productsin the balance of the intestinal microbiota due not only to theaction of the probiotics but also to the potential modulationeffects exerted by polyphenols as it has been described in thisreview Further research in this area will aim to accomplishthe benefits of both probiotic strains and polyphenols inrelation to gut health

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors of this review were funded by the SpanishMINECO through different projects (AGL2012-40172-C02-01 AGL2010-17499 and BFU2012-35228) and the CON-SOLIDER INGENIO 2010 programme (project FUN-C-FOOD CSD2007-063) as well as Comunidad de Madrid(project ALIBIRD P2009AGR-1469) Montserrat Duenaswould like to thank the Spanish ldquoRamon y Cajalrdquo Programmefor a contract

References

[1] S E Power P W OrsquoToole C Stanton R P Ross and GF Fitzgerald ldquoIntestinal microbiota diet and healthrdquo BritishJournal of Nutrition vol 111 no 3 pp 387ndash402 2014

[2] PDeCruz L Prideaux JWagner et al ldquoCharacterization of thegastrointestinal microbiota in health and inflammatory boweldiseaserdquo Inflammatory Bowel Diseases vol 18 no 2 pp 372ndash390 2012

[3] A Kramer S Bekeschus B M Broker H Schleibinger BRazavi and O Assadian ldquoMaintaining health by balancingmicrobial exposure and prevention of infection the hygienehypothesis versus the hypothesis of early immune challengerdquoJournal of Hospital Infection vol 83 no 1 pp S29ndashS34 2013

[4] M Rescigno ldquoIntestinal microbiota and its effects on theimmune systemrdquo Cellular Microbiology vol 16 no 7 pp 1004ndash1013 2014

[5] M G L Hertog E J M Feskens P C H HollmanM B Katanand D Kromhout ldquoDietary antioxidant flavonoids and risk ofcoronary heart disease the Zutphen Elderly StudyrdquoThe Lancetvol 342 no 8878 pp 1007ndash1011 1993

[6] I C W Arts and P C H Hollman ldquoPolyphenols and diseaserisk in epidemiologic studiesrdquoThe American Journal of ClinicalNutrition vol 81 no 1 pp 317Sndash325S 2009

[7] D del Rio A Rodriguez-Mateos J P E Spencer M TognoliniG Borges and A Crozier ldquoDietary (poly)phenolics in humanhealth structures bioavailability and evidence of protectiveeffects against chronic diseasesrdquo Antioxidants amp Redox Signal-ing vol 18 no 14 pp 1818ndash1892 2013

[8] F Perez-Vizcaino and J Duarte ldquoFlavonols and cardiovasculardiseaserdquo Molecular Aspects of Medicine vol 31 no 6 pp 478ndash494 2010

[9] J P E Spencer K Vafeiadou R J Williams and D VauzourldquoNeuroinflammation modulation by flavonoids and mecha-nisms of actionrdquo Molecular Aspects of Medicine vol 33 no 1pp 83ndash97 2012

[10] J M Laparra and Y Sanz ldquoInteractions of gut microbiota withfunctional food components and nutraceuticalsrdquo Pharmacolog-ical Research vol 61 no 3 pp 219ndash225 2010

[11] X He M L Marco and C M Slupsky ldquoEmerging aspects offood and nutrition on gut microbiotardquo Journal of Agriculturaland Food Chemistry vol 61 no 40 pp 9559ndash9574 2013

[12] D Hervert-Hernandez and I Goni ldquoDietary polyphenols andhuman gut microbiota a reviewrdquo Food Reviews Internationalvol 27 no 2 pp 154ndash169 2011

[13] K M Tuohy L Conterno M Gasperotti and R Viola ldquoUp-regulating the human intestinal microbiome using whole plantfoods polyphenols andor fiberrdquo Journal of Agricultural andFood Chemistry vol 60 no 36 pp 8776ndash8782 2012

[14] U Etxeberria A Fernandez-Quintela F I Milagro L AguirreJ A Martınez and M P Portillo ldquoImpact of polyphenols andpolyphenol-rich dietary sources on gut microbiota composi-tionrdquo Journal of Agricultural and Food Chemistry vol 61 no 40pp 9517ndash9533 2013

[15] F Cardona C Andres-Lacueva S Tulipani F J Tinahonesand M I Queipo-Ortuno ldquoBenefits of polyphenols on gutmicrobiota and implications in human healthrdquo Journal ofNutritional Biochemistry vol 24 no 8 pp 1415ndash1422 2013

[16] M V Selma J C Espın and F A Tomas-Barberan ldquoInteractionbetween phenolics and gut microbiota role in human healthrdquoJournal of Agricultural and Food Chemistry vol 57 no 15 pp6485ndash6501 2009

[17] T RequenaMMonagasM A Pozo-Bayon et al ldquoPerspectivesof the potential implications ofwine polyphenols on humanoraland gut microbiotardquo Trends in Food Science amp Technology vol21 no 7 pp 332ndash344 2010

[18] J Van Duynhoven E E Vaughan F van Dorsten et alldquoInteractions of black tea polyphenols with human gut micro-biota implications for gut and cardiovascular health1-4rdquo TheAmerican Journal of Clinical Nutrition vol 98 no 6 pp 1631Sndash1641S 2013

[19] SMoco F-P JMartin and S Rezzi ldquoMetabolomics view on gutmicrobiome modulation by polyphenol-rich foodsrdquo Journal ofProteome Research vol 11 no 10 pp 4781ndash4790 2012

BioMed Research International 13

[20] R K Buddington and P T Sangild ldquoCompanion animalssymposium development of the mammalian gastrointestinaltract the resident microbiota and the role of diet in early liferdquoJournal of Animal Science vol 89 no 5 pp 1506ndash1519 2011

[21] K Tiihonen A C Ouwehand and N Rautonen ldquoHumanintestinal microbiota and healthy ageingrdquo Ageing ResearchReviews vol 9 no 2 pp 107ndash116 2010

[22] D Mariat O Firmesse F Levenez et al ldquoThe firmicutesbacteroidetes ratio of the human microbiota changes with agerdquoBMCMicrobiology vol 9 article 123 2009

[23] M Arumugam J Raes E Pelletier et al ldquoEnterotypes of thehuman gutmicrobiomerdquoNature vol 473 no 7346 pp 174ndash1802011

[24] G D Wu J Chen C Hoffmann et al ldquoLinking long-termdietary patterns with gut microbial enterotypesrdquo Science vol334 no 6052 pp 105ndash108 2011

[25] I B JefferyM J Claesson PWOrsquoToole and F Shanahan ldquoCat-egorization of the gut microbiota enterotypes or gradientsrdquoNature Reviews Microbiology vol 10 no 9 pp 591ndash592 2012

[26] WM de Vos andM Nieuwdorp ldquoGenomics a gut predictionrdquoNature vol 498 no 7452 pp 48ndash49 2013

[27] P B Eckburg E M Bik C N Bernstein et al ldquoMicrobiologydiversity of the human intestinal microbial florardquo Science vol308 no 5728 pp 1635ndash1638 2005

[28] E G Zoetendal C T Collier S Koike R I Mackie and H RGaskins ldquoMolecular ecological analysis of the gastrointestinalmicrobiota a reviewrdquo Journal of Nutrition vol 134 no 2 pp465ndash472 2004

[29] M H Fraher PW OrsquoToole and E MM Quigley ldquoTechniquesused to characterize the gut microbiota a guide for the clini-cianrdquo Nature Reviews Gastroenterology and Hepatology vol 9no 6 pp 312ndash322 2012

[30] R A Kemperman S Bolca L C Roger and E E VaughanldquoNovel approaches for analysing gut microbes and dietarypolyphenols challenges and opportunitiesrdquo Microbiology vol156 no 11 pp 3224ndash3231 2010

[31] R A Kemperman G Gross S Mondot et al ldquoImpact ofpolyphenols from black tea and red winegrape juice on a gutmodel microbiomerdquo Food Research International vol 53 no 2pp 659ndash669 2013

[32] M N Clifford ldquoDiet-derived phenols in plasma and tissues andtheir implications for healthrdquo Planta Medica vol 70 no 12 pp1103ndash1114 2004

[33] A Crozier D del Rio and M N Clifford ldquoBioavailability ofdietary flavonoids and phenolic compoundsrdquoMolecular Aspectsof Medicine vol 31 no 6 pp 446ndash467 2010

[34] A J Day M S Dupont S Ridley et al ldquoDeglycosylation offlavonoid and isoflavonoid glycosides by human small intestineand liver beta-glucosidase activityrdquo FEBS Letters vol 436 no 1pp 71ndash75 1998

[35] A J Day F J Canada J C Dıaz et al ldquoDietary flavonoid andisoflavone glycosides are hydrolysed by the lactase site of lactasephlorizin hydrolaserdquo FEBS Letters vol 468 no 2-3 pp 166ndash1702000

[36] A Scalbert and G Williamson ldquoDietary intake and bioavail-ability of polyphenolsrdquo Journal of Nutrition vol 130 no 8 pp2073Sndash2085S 2000

[37] A R Rechner G Kuhnle H Hu et al ldquoThe metabolism ofdietary polyphenols and the relevance to circulating levels ofconjugated metabolitesrdquo Free Radical Research vol 36 no 11pp 1229ndash1241 2002

[38] A-M Aura K A OrsquoLeary G Williamson et al ldquoQuercetinderivatives are deconjugated and converted to hydroxypheny-lacetic acids but not methylated by human fecal flora in vitrordquoJournal of Agricultural and Food Chemistry vol 50 no 6 pp1725ndash1730 2002

[39] A-M Aura ldquoMicrobial metabolism of dietary phenolic com-pounds in the colonrdquo Phytochemistry Reviews vol 7 no 3 pp407ndash429 2008

[40] M Monagas M Urpi-Sarda F Sanchez-Patan et al ldquoInsightsinto themetabolism andmicrobial biotransformation of dietaryflavan-3-ols and the bioactivity of their metabolitesrdquo Food andFunction vol 1 no 3 pp 233ndash253 2010

[41] GWilliamson andMNClifford ldquoColonicmetabolites of berrypolyphenols the missing link to biological activityrdquo BritishJournal of Nutrition vol 104 no 3 pp S48ndashS66 2010

[42] D M Jacobs E Gaudier J van Duynhoven and E E VaughanldquoNon-digestible food ingredients colonic microbiota and theimpact on gut health and immunity a role for metabolomicsrdquoCurrent Drug Metabolism vol 10 no 1 pp 41ndash54 2009

[43] S Bolca S Possemiers V Maervoet et al ldquoMicrobial anddietary factors associatedwith the 8-prenylnaringenin producerphenotype a dietary intervention trial with fifty healthy post-menopausal Caucasian womenrdquo British Journal of Nutritionvol 98 no 5 pp 950ndash959 2007

[44] X Tzounis J Vulevic G G C Kuhnle et al ldquoFlavanolmonomer-induced changes to the human faecal microflorardquoBritish Journal of Nutrition vol 99 no 4 pp 782ndash792 2008

[45] M Hidalgo M J Oruna-Concha S Kolida et al ldquoMetabolismof anthocyanins by human gut microflora and their influenceon gut bacterial growthrdquo Journal of Agricultural and FoodChemistry vol 60 no 15 pp 3882ndash3890 2012

[46] A L Molan M A Lila J Mawson and S De ldquoIn vitroand in vivo evaluation of the prebiotic activity of water-soluble blueberry extractsrdquo World Journal of Microbiology andBiotechnology vol 25 no 7 pp 1243ndash1249 2009

[47] D Bialonska P Ramnani S G Kasimsetty K R Muntha GR Gibson and D Ferreira ldquoThe influence of pomegranate by-product and punicalagins on selected groups of human intesti-nal microbiotardquo International Journal of FoodMicrobiology vol140 no 2-3 pp 175ndash182 2010

[48] G Mandalari R M Faulks C Bisignano K W Waldron ANarbad and M S J Wickham ldquoIn vitro evaluation of theprebiotic properties of almond skins (Amygdalus communisL)rdquoFEMS Microbiology Letters vol 304 no 2 pp 116ndash122 2010

[49] V Fogliano M L Corollaro P Vitaglione et al ldquoIn vitro bioac-cessibility and gut biotransformation of polyphenols present inthe water-insoluble cocoa fractionrdquoMolecular Nutritionamp FoodResearch vol 55 supplement 1 pp S44ndashS55 2011

[50] M J Pozuelo A Agis-Torres D Hervert-Hernandez etal ldquoGrape antioxidant dietary fiber stimulates Lactobacillusgrowth in rat cecumrdquo Journal of Food Science vol 77 no 2 ppH59ndashH62 2012

[51] C Cueva F Sanchez-Patan M Monagas et al ldquoIn vitrofermentation of grape seed flavan-3-ol fractions by humanfaecal microbiota changes in microbial groups and phenolicmetabolitesrdquo FEMSMicrobiology Ecology vol 83 no 3 pp 792ndash805 2013

[52] F Sanchez-Patan C CuevaMMonagas et al ldquoIn vitro fermen-tation of a red wine extract by human gut microbiota changesin microbial groups and formation of phenolic metabolitesrdquoJournal of Agricultural and Food Chemistry vol 60 no 9 pp2136ndash2147 2012

14 BioMed Research International

[53] E Barroso F Sanchez-Patan P J Martın-Alvarez et al ldquoLacto-bacillus plantarum IFPL935 favors the initial metabolism of redwine polyphenols when added to a colonic microbiotardquo Journalof Agricultural and Food Chemistry vol 61 no 42 pp 10163ndash10172 2013

[54] G R Gibson J H Cummings and G T Macfarlane ldquoUse ofa three-stage continuous culture system to study the effect ofmucin on dissimilatory sulfate reduction and methanogenesisby mixed populations of human gut bacteriardquo Applied andEnvironmentalMicrobiology vol 54 no 11 pp 2750ndash2755 1988

[55] KMollyMVandeWoestyne andWVerstraete ldquoDevelopmentof a 5-step multi-chamber reactor as a simulation of thehuman intestinal microbial ecosystemrdquo Applied Microbiologyand Biotechnology vol 39 no 2 pp 254ndash258 1993

[56] M Minekus M Smeets-Peeters A Bernalier et al ldquoAcomputer-controlled system to simulate conditions of thelarge intestine with peristaltic mixing water absorption andabsorption of fermentation productsrdquoAppliedMicrobiology andBiotechnology vol 53 no 1 pp 108ndash114 1999

[57] PDeBoever BDeplancke andWVerstraete ldquoFermentation bygut microbiota cultured in a simulator of the human intestinalmicrobial ecosystem is improved by supplementing a soygermpowderrdquo Journal of Nutrition vol 130 no 10 pp 2599ndash26062000

[58] C S Yang X Wang G Lu and S C Picinich ldquoCancerprevention by tea animal studies molecular mechanisms andhuman relevancerdquoNature Reviews Cancer vol 9 no 6 pp 429ndash439 2009

[59] R E Ley F Backhed P Turnbaugh C A Lozupone R DKnight and J I Gordon ldquoObesity alters gut microbial ecologyrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 102 no 31 pp 11070ndash11075 2005

[60] H Hara N Orita S Hatano et al ldquoEffect of tea polyphenols onfecal flora and fecal metabolic products of pigsrdquo The Journal ofVeterinary Medical Science vol 57 no 1 pp 45ndash49 1995

[61] N Ishihara D-C Chu S Akachi and L R Juneja ldquoImprove-ment of intestinal microflora balance and prevention of diges-tive and respiratory organ diseases in calves by green teaextractsrdquo Livestock Production Science vol 68 no 2-3 pp 217ndash229 2001

[62] P Dolara C Luceri C De Filippo et al ldquoRed wine polyphenolsinfluence carcinogenesis intestinal microflora oxidative dam-age and gene expression profiles of colonicmucosa in F344 ratsrdquoMutation Research-Fundamental and Molecular Mechanisms ofMutagenesis vol 591 no 1-2 pp 237ndash246 2005

[63] S Sembries G Dongowski K Mehrlander F Will and HDietrich ldquoPhysiological effects of extraction juices from applegrape and red beet pomaces in ratsrdquo Journal of Agricultural andFood Chemistry vol 54 no 26 pp 10269ndash10280 2006

[64] S Sembries G Dongowski G Jacobasch K Mehrlander FWill andH Dietrich ldquoEffects of dietary fibre-rich juice colloidsfrom apple pomace extraction juices on intestinal fermentationproducts and microbiota in ratsrdquo British Journal of Nutritionvol 90 no 3 pp 607ndash615 2003

[65] A Viveros S Chamorro M Pizarro I Arija C Centeno andA Brenes ldquoEffects of dietary polyphenol-rich grape productson intestinal microflora and gut morphology in broiler chicksrdquoPoultry Science vol 90 no 3 pp 566ndash578 2011

[66] A H Smith and R I Mackie ldquoEffect of condensed tannins onbacterial diversity andmetabolic activity in the rat gastrointesti-nal tractrdquo Applied and Environmental Microbiology vol 70 no2 pp 1104ndash1115 2004

[67] M Massot-Cladera T Perez-Berezo A Franch M Castelland F J Perez-Cano ldquoCocoa modulatory effect on rat faecalmicrobiota and colonic crosstalkrdquo Archives of Biochemistry andBiophysics vol 527 no 2 pp 105ndash112 2012

[68] M Larrosa M J Yanez-Gascon M V Selma et al ldquoEffectof a low dose of dietary resveratrol on colon microbiotainflammation and tissue damage in a DSS-induced colitis ratmodelrdquo Journal of Agricultural and Food Chemistry vol 57 no6 pp 2211ndash2220 2009

[69] A-L Molan Z Liu andM Kruger ldquoThe ability of blackcurrantextracts to positively modulate key markers of gastrointestinalfunction in ratsrdquoWorld Journal ofMicrobiologyampBiotechnologyvol 26 no 10 pp 1735ndash1743 2010

[70] A Lacombe R W Li D Klimis-Zacas et al ldquoLowbush wildblueberries have the potential to modify gut microbiota andxenobiotic metabolism in the rat colonrdquo PLoS ONE vol 8 no6 Article ID e67497 2013

[71] R Saad M R Rizkallah and R K Aziz ldquoGut Pharmacomicro-biomics the tip of an iceberg of complex interactions betweendrugs and gut-associated microbesrdquo Gut Pathogens vol 4 no1 article 16 2012

[72] E J J Van Velzen J A Westerhuis J P M van Duynhovenet al ldquoMultilevel data analysis of a crossover designed humannutritional intervention studyrdquo Journal of Proteome Researchvol 7 no 10 pp 4483ndash4491 2008

[73] T Okubo N Ishihara H Takahashi et al ldquoEffects of partiallyhydrolyzed guar gum intake on human intestinal microfloraand itsmetabolismrdquoBioscience Biotechnology andBiochemistryvol 58 no 8 pp 1364ndash1369 1994

[74] V Mai H A Katki H Harmsen et al ldquoEffects of a controlleddiet and black tea drinking on the fecalmicroflora compositionand the fecal bile acid profile of human volunteers in a double-blinded ramdomized feeding studyrdquo The Journal of Nutritionvol 134 no 2 pp 473ndash478 2004

[75] J-S Jin M Touyama T Hisada and Y Benno ldquoEffectsof green tea consumption on human fecal microbiota withspecial reference to Bifidobacterium speciesrdquoMicrobiology andImmunology vol 56 no 11 pp 729ndash739 2012

[76] J Yamakoshi S Tokutake M Kikuchi Y Kubota H Konishiand T Mitsuoka ldquoEffect of proantocyanidin -rich extract fromgrape seed on human fecal flora and fecalodorrdquo FASEB Journalvol 15 no 4 p A633 2001

[77] X Tzounis A Rodriguez-Mateos J Vulevic G R Gibson CKwik-Uribe and J P E Spencer ldquoPrebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomizedcontrolled double-blind crossover intervention studyrdquo TheAmerican Journal of Clinical Nutrition vol 93 no 1 pp 62ndash722011

[78] M I Queipo-Ortuno M Boto-Ordonez M Murri et alldquoInfluence of red wine polyphenols and ethanol on the gutmicrobiota ecology and biochemical biomarkersrdquo AmericanJournal of Clinical Nutrition vol 95 no 6 pp 1323ndash1334 2012

[79] K Shinohara Y Ohashi K Kawasumi A Terada and TFujisawa ldquoEffect of apple intake on fecal microbiota andmetabolites in humansrdquo Anaerobe vol 16 no 5 pp 510ndash5152010

[80] C I R Gill G J Mcdougall S Glidewell et al ldquoProfiling ofphenols in human fecal water after raspberry supplementationrdquoJournal of Agricultural and Food Chemistry vol 58 no 19 pp10389ndash10395 2010

[81] S Vendrame S Guglielmetti P Riso S Arioli D Klimis-Zacasand M Porrini ldquoSix-week consumption of a wild blueberry

BioMed Research International 15

powder drink increases Bifidobacteria in the human gutrdquoJournal of Agricultural and Food Chemistry vol 59 no 24 pp12815ndash12820 2011

[82] S Guglielmetti D Fracassetti V Taverniti et al ldquoDifferentialmodulation of human intestinal Bifidobacterium populationsafter consumption of a wild blueberry (Vaccinium angusti-folium) drinkrdquo Journal of Agricultural and Food Chemistry vol61 no 34 pp 8134ndash8140 2013

[83] T Clavel M Fallani P Lepage et al ldquoIsoflavones and func-tional foods alter the dominant intestinal microbiota in post-menopausal womenrdquo Journal of Nutrition vol 135 no 12 pp2786ndash2792 2005

[84] A Costabile A Klinder F Fava et al ldquoWhole-grain wheatbreakfast cereal has a prebiotic effect on the human gut micro-biota a double-blind placebo-controlled crossover studyrdquoBritish Journal of Nutrition vol 99 no 1 pp 110ndash120 2008

[85] A L Carvalho-Wells K Helmolz C Nodet et al ldquoDetermina-tion of the in vivo prebiotic potential of a maize-based wholegrain breakfast cereal a human feeding studyrdquo British Journalof Nutrition vol 104 no 9 pp 1353ndash1356 2010

[86] A Cuervo L Valdes N Salazar et al ldquoPilot study of diet andmicrobiota interactive associations of fibers and polyphenolswith human intestinal bacteriardquo Journal of Agricultural andFood Chemistry vol 62 no 23 pp 5330ndash5336 2014

[87] M Jaquet I Rochat J Moulin C Cavin and R BibilonildquoImpact of coffee consumption on the gut microbiota a humanvolunteer studyrdquo International Journal of FoodMicrobiology vol130 no 2 pp 117ndash121 2009

Submit your manuscripts athttpwwwhindawicom

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Page 3: Review Article A Survey of Modulation of Gut Microbiota by ...downloads.hindawi.com/journals/bmri/2015/850902.pdf · Review Article A Survey of Modulation of Gut Microbiota by Dietary

BioMed Research International 3

in the gut lumen The acquisition of gut microbiota beginsat birth and is strongly influenced by a range of factorsthat include host genetics immunological factors antibioticusage and also dietary habits [20] The microbial content ofthe gastrointestinal tract changes along its length rangingfrom a narrow diversity and low numbers of microbes inthe stomach to a wide diversity and high numbers in thelarge intestine which can reach 1012 CFUmL [21] Most ofintestinal bacteria belong to phylum Firmicutes (includingClostridium Enterococcus Lactobacillus and Ruminococcusgenera) and Bacteroidetes (including Prevotella and Bac-teroides genera) which constitute over 90 of known phy-logenetic categories and dominate the distal gut microbiota[22] Recently a novel classification of microbiota into threepredominant ldquoenterotypesrdquo dominated by three differentgenera Bacteroides Prevotella and Ruminococcus has beensuggested [23] In this line Wu et al [24] demonstratedthat long-term diet high in animal proteins and fats versussimple carbohydrates clustered the human subjects into thepreviously described enterotypes Bacteroides and PrevotellaHowever there is a current debate if the enterotypes shouldbe seen discontinuous or as a gradient [25] But in any casea common observation is that homeostasis and resilience arecoupled to a highly diverse gut microbiota in healthy peoplewhereas inflammatory and metabolic disorders are linked toperturbations in the composition andor functions of the gutmicrobiota [26]

Culture-based techniques employed to bacteria identifi-cation are fairly cheap laborious and time-consuming andgives a limited view of the diversity and dynamics of thegastrointestinal microbiota with less than 30 of gut micro-biotamembers having been cultured to date [27] Since 1990sthe introduction of novel molecular biological procedureshas made it possible to overcome some of these limitationswith the use of culture-independent methods [28] Theseprocedures are based on sequence divergences of the smallsubunit ribosomal RNA (16S rRNA) and include techniquessuch as denaturing gradient gel electrophoresis (DGGE)terminal restriction fragment length polymorphism (T-RFLP) fluorescence in situ hybridization (FISH) quantitativepolymerase chain reaction (qPCR) DNA microarrays andnext-generation sequencing (NGS) of the 16S rRNA geneor its amplicons [29] NGS techniques have promoted theemergence of new high-throughput technologies such asgenomics metagenomics transcriptomics and metatran-scriptomics Metagenomics gives a more in-depth unbiasedmicrobial analysis beyond the group level and involvesmultiple species besides showing shorter sequencing speedextended read length and lower costs [30] However theenormous amount of data generated becomes cumbersome toanalyze and requires lots of dedicated time as well as expertiseto manage [29]

In the context of polyphenol-microbiota interactions theemerging high-throughput meta-genomic transcriptomicand proteomic approaches can be adopted to identify genesand micro-organisms involved in polyphenol (in)activationand conversion to reconstruct metabolic pathways and tomonitor how microbial communities adjust their metabolic

activities upon polyphenol exposure [30] Application ofthese technologies to human fecal samples requires fur-ther investigation to determine how these samples reflectmetabolism inside the gut and ultimately to improve theunderstanding of the impact of polyphenols on host health[12 31]

3 Dietary Polyphenols

It has been estimated that 90ndash95 of dietary polyphenols arenot absorbed in the small intestine and therefore reach thecolon [32] although absorption and metabolism are largelyinfluenced by their chemical structure Most flavonoids arepoorly absorbed from the small intestine and are highlymetabolized in the large intestine Isoflavones seem to bethe best absorbed dietary flavonoids catechins flavanonesand flavonol glycosides are intermediate whereas proantho-cyanidins flavan-3-ol gallates and anthocyanins would bethe worst absorbed [33]

The first step in the metabolism of flavonoids with theexception of flavan-3-ols (ie catechins and proanthocyani-dins) is likely to be deglycosylation before absorption inthe small intestine Hydrolysis of some flavonoid glycosidemight already occur in the oral cavity as both saliva andoral microbiota show 120573-glucosidase activity But the mech-anism most usually assumed for flavonoid deglycosylation ishydrolysis by lactase phlorizin hydrolase (LPH) in the brush-border of the small intestine epithelial cells [34 35] so thatthe resulting aglycones would enter the enterocyte by passivediffusion The resulting aglycone is rapidly biotransformedby phase II enzymes within the enterocyte and further inthe liver so that conjugated metabolites (ie glucuronidesO-mehtylethers andor sulphates) through the respectiveaction of UDP-glucuronosyltransferase (UGT) catechol-O-methyltransferase (COMT) and sulphotransferases would bethe circulating forms in the human body [36 37]

Generally a relevant fraction of dietary flavonoids isnot absorbed in the small intestine and together withthe conjugated metabolites that returned to the intestinallumen via enterohepatic circulation reaches the large intes-tine where compounds are subjected to the action of thecolonic microbiota Intestinal bacteria show diverse degly-cosylating activities thus releasing aglycones that might beabsorbed in a lesser extent and more probably degradedto simpler phenolic derivatives [38 39] Degradation offlavonoid aglycones by colonic microbiota involves ring-C cleavage and reactions affecting functional groups suchas dehydroxylation demethylation or decarboxylation [39]Various hydroxylated aromatic compounds derived from theA-ring (eg phloroglucinol 34-dihydroxybenzaldehyde or34-dihydroxytoluene) and phenolic acids derived from theB-ring have been reported as relevant products of the colonictransformation of flavonoids [40] It has become evidentthat the beneficial effects attributed to dietary polyphenolsappear to be due more to phenolic metabolites formed in thegastrointestinal tract mainly derived from the action of gutbacteria rather than to the original forms found in food [41]

In subsequent sections main findings related to themodulation of gut microbiota by polyphenols are presented

4 BioMed Research International

as obtained from different methodological approaches andmicrobial analysis techniques

4 Studies Using Batch Culture Fermentations

Although in vivo human or animal intervention trials arephysiologically most relevant to study both polyphenolmetabolism and microbial modulation in vitro tools havebeen designed to simulate intestinal conditions In combi-nation with in vivo trials in vitro experiments may help toelucidate the extent bioconversion processes mediated by thehost itself [42 43] The complexity of in vitro gut models isdiverse ranging from simple static models (batch culture fer-mentation) to advanced continuous models (gastrointestinalsimulators)

Simple static gut models also known as batch-typecultures are generally closed systems using sealed bottlesor reactors containing suspensions of fecal material that aremaintained under anaerobic conditions They are relativelyeasy to operate and cost-effective have a fair throughputand allow for parallel screening This model approach isprimarily used to assess the stability of polyphenols in thepresence of human-derived gut microbiota and to evaluatewhich environmental conditions favor or limit polyphenolbioconversion However these static gut models are onlyadequate for simulating short-term conditions in the gutfor assessment of long-term adaptations of the gut microbialcommunity more complex dynamic models are needed[12]

Table 1 reports different studies of modulation of gutmicrobiota by dietary polyphenols using batch-type culturesDetails about fermentation conditions (fecal concentrationpolyphenol origin and dose and incubation time) andmicro-bial techniques used and main effects on bacteria groups(growth enhancement growth inhibition or no effect) havebeen included As general characteristics fecal fermentationsemployed feces concentration le10 (wv) and lasted 48 hmaximum Both pure phenolic compounds and phenolic-rich extracts were added to the fecal medium at a finalconcentration lt10 (wv) and changes in specific bacterialgroups weremainly assessed by FISH analysis A first relevantexperiment using batch culture fermentation was carriedout by Tzounis et al [44] who found that the flavan-3-olmonomers [(minus)-epicatechin and (+)-catechin] promoted thegrowth of Clostridium coccoides-Eubacterium rectale groupwhich is known to produce large amounts of butyrate a short-chain fatty acid (SCFA) with anti-inflammatory and anti-neoplasic properties (+)-catechin also increased the growthof Lactobacillus-Enterococcus spp Bifidobacterium spp andEscherichia coli but decreased the growth of Clostridiumhistolyticum Also using standard compounds Hidalgo et al[45] found that anthocyanins (ie malvidin-3-glucoside andamixture of anthocyanins) significantly enhanced the growthof Lactobacillus-Enterococcus spp and Bifidobacterium sppIn addition malvidin-3-glucoside showed a tendency topromote the growth of the C coccoides-E rectale group

Similar results have been observed in batch culturefermentations with phenolic-rich extracts from different

sourcesMolan et al [46] found that the addition of blueberryextracts to a mixture of fecal bacterial populations signifi-cantly increased the number of lactobacilli and bifidobacteria(Table 1) In the same line Bialonska et al [47] reportedenhancement of the growth of total bacteria Bifidobacteriumspp and Lactobacillus-Enterococcus spp in response to acommercial extract of pomegranate without influencing theC coccoides-E rectale and C histolyticum groups (Table 1)Mandalari et al [48] suggested a potential prebiotic effectfor natural and blanched almond skins as these foodstuffs infermentations with fecal microbiota significantly increasedthe populations of bifidobacteria and C coccoides-E rectalegroup and decreased the number of C hystolyticum groupThese authors related the possible prebiotic effect by almondskins not only to a high amount of dietary fibre but also tosome phenolic compounds such as ferulic acid flavan-3-olsand flavonols present in the almond skins [48] Fogliano et al[49] carried out an in vitro fermentation with a water-insoluble cocoa fraction in a three-stage continuous culturecolonicmodel system It was observed that this cocoa fractionpresented prebiotic activity producing a significant increasein lactobacilli and bifidobacteria as well as an increase inbutyrate production They concluded that the coexistenceof fermentable polysaccharides and free flavanol monomersin cocoa such as catechins might be very effective in themodification of gut microbiota Similar conclusions weredrawn by Pozuelo et al [50] who found a significant increaseof the growth of Lactobacillus reuteri and Lactobacillusacidophilus in the presence of a grape antioxidant dietary fibernaturally obtained from red grapes Our research group car-ried out several batch culture fermentations of two flavan-3-ol fractions with different degree of polymerisation and winepolyphenols with fecal microbiota from different healthyvolunteers [51 52] Both flavan-3-ol fractions promoted thegrowth ofLactobacillusEnterococcus spp and inhibited theChistolyticum group during fermentation although the effectswere only statistically significant with the less polymerizedfractionWine polyphenols only showed a slight inhibition intheC histolyticum group probably due to their lower contentin flavan-3-ols

Additionally this type of fermentations has also beenused to assess the contribution of certain probiotic strainsto the colonic metabolism of polyphenols In this senseBarroso et al [53] carried out fermentations of a red wineextract inoculated with human microbiota obtained fromthe colonic compartments of a dynamic simulator in thepresence and absence of the probiotic strain L plantarumIFPL935 Microbial analysis by qPCR indicated that redwine polyphenols induced greater variations among in vitrobatches harboring different colon-region (ascending colondescending colon and effluent) microbiota than those foundwhen L plantarum IFPL935 was added Batches inoculatedwith microbiota from the ascending colon were shown toharbor the major proportion of saccharolytic bacteria (Bac-teroides Bifidobacterium and Prevotella) whereas Clostrid-ium groups were found in major numbers in the batchesinoculated with microbiota simulating the distal regions [53](Table 1)

BioMed Research International 5

Table1Stud

iesu

singbatchcultu

referm

entatio

n

Reference

Fecal

concentration

Phenolic

compo

undfood

Dose

Timeo

fincubatio

nMicrobial

techniqu

eGrowth

enhancem

ent

Growth

inhibitio

nNoeffect

Tzou

nise

tal

(2008)

[44]

10w

v(+)-catechin

150m

gL

1000

mgL

lt48

hFISH

Lactobacillus-

Enterococcus

spp

Bifid

obacteriu

mspp

Ccoccoides-E

rectale

grou

pE

coli

Chisto

lyticum

grou

p

Molan

etal(2009)

[46]

01

vv

Blueberryextracts

510

and25

48h

FISH

Lactob

acilli

Bifid

obacteria

Bialon

skae

tal

(2010)

[47]

10w

vPo

megranate

extractand

punicalagin

10

48h

FISH

Totalbacteria

Bifid

obacteriu

mspp

Lactobacillus-

Enterococcus

spp

Ccoccoides-E

rectale

grou

pC

histo

lyticum

grou

p

Mandalarietal

(2010)

[48]

10w

vAlm

ondskins

1w

vpredigested

almon

dskins

lt24

hFISH

Bifid

obacteria

Ccoccoides-E

rectale

grou

p

Chisto

lyticum

grou

p

Fogliano

etal

(2011)[49]

5w

vWater-in

soluble

cocoafraction

1w

v36

hFISH

Bifid

obacteria

Lactob

acilli

Cuevae

tal(2013)

[51]

10w

vGrape

seed

extract

fractio

ns300ndash

450m

gL

lt48

hFISH

Lactobacillus-

Enterococcus

spp

Chisto

lyticum

grou

p

Hidalgo

etal

(2012)

[45]

10w

v

Malvidin-3-O-

glucoside

Antho

cyanidins

mixture

20mgLand

200m

gL

4850

mgLand

48500m

gL

lt24

hFISH

Lactobacillus-

Enterococcus

spp

Bifid

obacteriu

mspp

Ccoccoides-E

rectale

grou

p

Sanchez-Patanet

al(2012)[52]

1wv

Redwinee

xtract

600m

gL

48h

FISH

Chisto

lyticum

grou

p

Lactobacillus-

Enterococcus

spp

Barrosoetal

(2013)

[53]

Redwinee

xtract

500m

gL

48h

qPCR

Lactobacillus

spp

Bifid

obacteriu

mspp

Bacteroidesspp

Ru

minococcusspp

6 BioMed Research International

Table 2 Studies using the gastrointestinal simulators (ie SHIME)

Reference Simulator Phenoliccompoundfood Dose Time Microbial

techniquePopulationincrease Population decrease

De Boeveret al (2000)[57]

SHIME Soy germ powder 25 gday 2 weeks Plate count

EnterobacteriaceaeColiforms

Lactobacillus sppStaphylococcus sppClostridium spp

Kempermanet al (2013)[31]

Twin-SHIME Black tea extract

3 times dailydosing(1000mg

polyphenolsas total daily

dose)

2 weeks

Plate countqPCR

PCR-DGGEpyrosequencing

Klebsiella sppEnterococci

Akkermansia spp

BifidobacteriaBlautia coccoidesAnaeroglobus sppVictivallis spp

Kempermanet al (2013)[31]

Twin-SHIME

Red wine-grapeextract

3 times dailydosing(1000mg

polyphenolsas total daily

dose)

2 weeks

Plate countqPCR

PCR-DGGEpyrosequencing

Klebsiella sppAlistipes spp

Cloacibacillus sppVictivallis spp

Akkermansia spp

BifidobacteriaBlautia coccoides

groupAnaeroglobus spp

Subdoligranulum sppBacteroides

5 Studies Using HumanGastrointestinal Simulators

In contrast to short-duration experiments with static gutmodels longer-term experiments are required when theadaptation of the gut microbial community to dietarypolyphenols needs to be assessed To this end dynamic invitro gut models such as the ldquoReadingrdquo model [54] theSimulator of the Human Intestinal Microbial Ecosystem(SHIME) the TNO Intestinal Model 2 (TIM2) [55 56] andthe recent gastrointestinal simulator set up in our Institute(SIMGI) (unpublished work) have been developed where gutmicrobiota are cultured over a longer time frame (days toweeks) in one or multiple connected pH controlled vesselsrepresenting different parts of the gastrointestinal tract

As an example of the versatility and potential of humangastrointestinal simulators Table 2 reports a series of studiesabout modulation of gut microbiota by polyphenols usingthe SHIME [57 58]This validatedmodel comprises stomachand small intestinal sections for predigestion of food aswell as vessels stimulating the ascending transcending anddescending parts of the human colon allowing assessment ofchanges in the different colonic areas that are very challengingto access in a human intervention However it should beunderlined that this approach takes for granted that theextracts reach intact the colonic region and no nutrientabsorption is consideredThe use of the SHIME to investigatethe effects of a soy germ powder on the fermentative capacityof the simulated microbiota of the colon was the aim of astudy carried out by De Boever et al [57]They observed thatthe addition of the soy germ powder in a 2-week treatmentresulted into an overall increase of bacterial marker pop-ulations (Enterobacteriaceae coliforms Lactobacillus sppStaphylococcus spp and Clostridium spp) with a significantincrease of 2 log10 units in the Lactobacillus spp populationMore recently Kemperman et al [31] using the twin-SHIME

model studied the influence of a bolus dose and a 2-weekcontinuous administration of complex dietary polyphenolsfrom black tea or red wine grape extracts on the colonicmicrobiota The Twin-SHIME system involving two modelsthat run in parallel was inoculatedwith the same fecal samplefor direct comparison of the effect of the two polyphenoltypes A combination of analyses including cultivation PCR-denaturing gradient gel electrophoresis (DGGE) quantita-tive PCR and high throughput pyrosequencing of the 16Sribosomal RNA gene was applied to characterize micro-bial community changes This study showed that complexpolyphenols in the context of a model system can modulateselect members of the human gut microbiota revealing noveltargets potentially involved in polyphenolmetabolism andorresistant microbes to be further investigated for polyphenolmetabolism or resistance mechanisms [31]

6 Animal Models Studies

It is widely assumed that preliminary evidence should bewarranted in animal models before human interventiontrials Animal models contribute to better understanding themechanisms and biological effects that could be likely tohappen in the human body The metabolism of polyphenolshas been object of numerous animal studies (mostly inrodents) especially for their impact on metabolic disorders[58] but only a few of these studies have followed thedynamics and composition of the intestinal microbiota inassociation with polyphenol metabolites retrieved from thehost Caution is required in extrapolating results to humansbecause culture-independent comparisons have revealed thatmost bacterial genera and species found in mice are not seenin humans although the distal gut microbiota of mice andhumans harbors the same bacterial phyla [59] In this sectionstudies performed in animals in order to assess the effects ofpolyphenols on the modulation of intestinal microbiota are

BioMed Research International 7

Table 3 Animal model studies

Reference Animal Phenoliccompoundfood Dose Treatment

durationMicrobialtechnique Population increase Population decrease

Hara et al(1995) [60] Pigs Tea polyphenols 02 (free access) 2 weeks Plate count Lactobacilli

Total bacteriaBacteroidaceaeC perfringens

Ishihara et al(2001) [61] Calves Green tea extracts 15 gday 4 weeks Plate count

Bifidobacterium sppLactobacillus sppC perfringens

Smith andMackie (2004)[66]

Rats

Proantocyanidinsextracted from

Acaciaangustissima

07 (low tannindiet) and 20

(high tannin diet)

35 weekstreatment +35 weekswashout

PCR-DGGEDot blot

hybridization

Bacteroides fragilisgroup

Bacteroides-Prevotella-

Porphyromonas group

Enterobacteriaceae

C leptum group

Dolara et al(2005) [62] Rats

Red winepolyphenolspowder

50mgkg 16 weeks Plate count LactobacilliBifidobacteria

PropionibacteriaBacteroidesClostridia

Sembries et al(2006) [63] Rats Apple juice free access 4 weeks Plate count Lactobacilli

BifidobacteriaSembries et al(2003) [64] Rats Apple pomace

juice colloid5 suppl diet(free access) 6 weeks Plate count

FISH Bacteroidaceae

Larrosa et al(2009) [68] Rats Resveratrol 1mgkgday 25 days Plate count Lactobacilli

Bifidobacteria

Molan et al(2010) [69] Rats

Blackcurrantextracts (leaf or

berry)

3 timesweek(i) 30mgkg

(leaf)(ii) 134mgkg

(berry)

4 weeks FISH

Lactobacilli (berryextract)

Bifidobacteria (leafand berry extracts)

Viveros et al(2011) [65]

Broilerchicks

Grape pomaceconcentrate(GPC) Grapeseed extract

(GSE)

60 gkg diet(GPC)

72 gkg diet(GSE)

(free access)

21 days Plate countT-RFLP

E coliEnterococcus sppLactobacillus spp

Lacombe et al(2013) [70] Rats Lowbush wild

blueberries

20 g feedday(eq 24 plusmn 52mganthocyaninday)

6 weeks Metagenomicsequencing

Thermonospora sppCorynebacteria spp

Slackia spp

Lactobacillus sppEnterococcus spp

summarized (Table 3) Experiments were mainly performedin rats although other larger animals such as chicks calvesor pigs have also been used Gut microbial communities wereevaluated by diverse methodologies including culture-basedmethods (plate count) DGGE FISH T-RFLP qPCR andmetagenomic sequencing

Animal studies performed in pigs [60] and in calves[61] demonstrated that tea polyphenols administration con-tributed to the improvement in the composition of the intesti-nal microbiota Thus the administration of tea polyphenolsin pigs significantly increased the levels of lactobacilli whilstit diminished the levels of total bacteria and Bacteroidaceaeand a tendency to decrease in lecithinase positive clostridiaincludingC perfringenswas also observed [60] However thereduction rate of Bifidobacterium spp and Lactobacillus sppwas slowwhile that ofC perfringensdecreased faster in calvessupplemented with the green tea extract [61]

Dolara et al [62] showed that treatment with winepolyphenols in carcinogen-treated F344 rats was associated

with a strong variation in the colonic microbiota comparedto the control-fed rats Although the total bacterial counts andanaerobeaerobe ratio of microorganisms in the feces frompolyphenol-treated rats were similar to that from control ratspropionibacteria Bacteroides and Clostridia decreased whilelactobacilli and bifidobacteria increased Based on additionalexperiments these authors concluded that reduction ofoxidative damage modulation of colonic flora and variationin gene expression may be all connected in the action of winepolyphenols on the intestinal function and carcinogenesis

In other study rats fedwith apple juice instead of drinkingwater showed more lactobacilli and bifidobacteria in freshfeces that differed from the controls by one-log10 colonyforming units [63] The same research group studied theeffect of colloids isolated from apple pomace extraction juiceson the intestinal microbiota in Wistar rats An increaseof Bacteroidaceae in almost one-log10 higher counts wasobserved in feces of rats fed with apple juice colloid thancontrol rats [64] Another animal experiment conducted to

8 BioMed Research International

study the effect on intestinal microbiota of the inclusionof grape pomace extracts in the diet of broiler chicks [65]found that for the cecum birds fed grape extracts had higherpopulations of E coli Lactobacillus and Enterococcus speciesthan birds in any other treatment group These authorsconcluded that grape polyphenol-rich products modified thegut morphology and intestinal microbiota and increased thebiodiversity degree of intestinal bacteria in broiler chicks

Inclusion of condensed tannins (proanthocyanidins)extracted from Acacia angustissima on rat diet resulted ina shift in the predominant bacteria towards tannin-resistantGram-negative Enterobacteriaceaeand Bacteroides speciesand reduced the number of Gram-positive C leptum group[66] Compatible results were obtained in an experimentwith rats fed a proanthocyanidin-rich cocoa preparation [67]where the authors found a significant decrease in the propor-tion of Bacteroides Clostridium and Staphylococcus generain the feces of cocoa-fed animals Interestingly reductions inClostridium species were found to correlate with weight lossand decrease in body mass index

Larrosa et al [68] observed an increase in lactobacilliand bifidobacteria when resveratrol (3541015840-trihydroxy-trans-stilbene) which naturally occurs in grapes and grape-derivedfoodstuffs such as red wine was administered to rats Afterinduction of colitis by dextran sulphate sodium proliferationof both E coli and enterobacteria was lower in rats treatedwith resveratrol than in control rats This could be the resultof an indirect effect of resveratrol-supplemented diet whichincreased bifidobacteria and lactobacilli counts preventingthe colonization and invasion of tissues by enterobacteriaincluding E coli

Prebiotic activity of wild blackcurrant extracts observedin in vitro experiments was further confirmed in rats byMolan et al [69] A significant increase in the populationsize of lactobacilli and bifidobacteria was observed after dailyadministration of those extracts to rats Similarly a grapeantioxidant dietary fibre preparation was found to increasethe population of Lactobacillus spp when fed to rats whereaspopulations of Bifidobacterium spp decreased and changes inE coli and Bacteroides vulgatus counts were not significant[50]

Recently Lacombe et al [70] studied the composition andfunctional potential of the colon microbiota from rats feda diet enriched in lowbush wild blueberries Application ofnovel metagenomic techniques (Illumina shotgun sequenc-ing) revealed a significant reduction in the relative abundanceof the genera Lactobacillus and Enterococcus associated withwild blueberries intake In addition hierarchical analysisshowed a significant increase in the relative abundanceof the phylum Actinobacteria the order Actinomycetalesand several novel genera under the family Bifidobacteri-aceae and Coriobacteriaceae in the blueberries group Theauthors indicated that although the microbiome of ratsdiffers from humans the applied model was a powerfultool to study population dynamics and related metabolicfunctions Metagenomic studies can determine microbialcommunity profiles gene presenceabsence and abundanceand functional repertoire however they can only infer an

observed phenotype since a gene presence does not imply itsexpression or functionality [71]

7 Human Intervention Studies

Investigations involving the use of humans potentially pro-vide the best models for studying the interactions of foodcomponents (eg polyphenols) with microbiota although invivo intervention trials hold inevitable practical and ethicallimitations [12] The use of cross-over designs where volun-teers serve as their own control permits multilevel analysisschemes that increase power but requires a relevant numberof volunteers to allow for statistically significant multivariatemodels [72] Up to now only a few studies have examinedthe in vivo impact of dietary polyphenols on the humangut microbiota and most of them were focused on singlepolyphenol molecules and selected bacterial populations Asummary of human intervention studies about effects ofpolyphenols in the modulation of the intestinal microbiotais collected in Table 4 In these studies the polyphenol doseused was much dependent on the type of food preparationand its concentration normally ranging from 01 to 4 thetreatment time was also variable from 10 days to 2 monthsand the applied microbial techniques were diverse (platecount DGGE FISH T-RFLP and qPCR)

In a study with a reduced number of subjects (119899 =8) Okubo et al [73] reported a notably increase in thepercentages of Bifidobacterium spp in total fecal countsafter an intervention with a product containing 70 of teapolyphenols A significant decrease of C perfringens andother Clostridium spp was also observed during the intakeperiod However in a crossover feeding study (number ofvolunteers not reported) that investigated the effects of blacktea drinking on hypercholesterolemic volunteers Mai et al[74] found that although specific bacterial groups were notaffected the total amount of bacteria significantly decreasedhighlighting large interindividual variations More recentlyan intervention study (119899 = 10) by Jin et al [75] confirmedan overall tendency for the proportion of bifidobacteria toincrease because of green tea consumption even thoughthere were interindividual differences in the Bifidobacteriumspecies

Yamakoshi et al [76] showed that administration of aproanthocyanidin-rich extract from grape seeds to healthyvolunteers (119899 = 9) significantly increased the fecal number ofBifidobacterium whereas the number of putrefactive bacteriasuch as enterobacteria tended to decrease The interactionbetween proanthocyanidins and intestinal bacteria was alsoconfirmed in a randomized double-blind crossover andcontrolled intervention study (119899 = 22) ingesting two cocoadrinks exhibiting low and high polyphenol content [77]Compared with the consumption of the low-flavan-3-olcocoa drink the daily consumption of the high-flavan-3-ol cocoa drink significantly increased the bifidobacteria andlactobacilli populations but significantly decreased clostridiacounts

Queipo-Ortuno et al [78] performed a randomizedcrossover and controlled trial (119899 = 10) consisting of theintake of red wine dealcoholized red wine and gin over

BioMed Research International 9

Table4Hum

aninterventio

nstu

dies

Reference

Volunteer

number

Phenolic

compo

undfood

Dose

Treatm

ent

duratio

nMicrobial

techniqu

ePo

pulatio

nincrease

Popu

latio

ndecrease

Noeffect

Oku

boetal

(1994)[73]

8Green

tea

(Sun

phenon

)04g

3tim

esper

day

4weeks

Platec

ount

Cperfr

ingens

Clostridium

spp

Yamakoshi

etal(2001)[76]

9Proantocyanidin-

richextractfrom

grapes

eeds

05g

day

6weeks

Platec

ount

Bifid

obacteriu

mspp

Enterobacteriaceae

Maietal

(200

4)[74]

15Blacktea

700m

gteas

olids5

times

perd

ay21

days

FISH

DGGE

Totalbacteria

Nochanges

Claveletal

(2005)

[83]

39Isofl

avon

es100m

gday

2mon

ths

TTGEFISH

Ccoccoides-E

rectale

grou

pBifid

obacteriu

mspp

Lactobacillus-

Enterococcus

spp

Faecalibacteriu

mprau

snitziisubgroup

Costabileetal

(2008)

[84]

31Who

legrainwheat

cereals

48gday

3weeks

FISH

Bifid

obacteria

Lactob

acilli

Totalbacteria

Bacteroidesspp

C

histo

lyticum

perfringens

grou

pAc

etobacteriu

mspp

Jaqu

etetal

(200

9)[87]

16Coff

ee3cupsday

3weeks

FISH

DGGE

Bifid

obacteriu

mspp

Carvalho

-Wellsetal

(2010)

[85]

32Who

legrainmaize

cereals

48gday

3weeks

FISH

Bifid

obacteria

Totalbacteria

Bacteroidesspp

C

histo

lyticum

perfringens

grou

pAc

etobacteriu

mspp

Gill

etal

(2010)

[80]

10Ra

spberrypu

ree

20gday

4days

PCR-DGGE

Nochangesinthep

rofileo

fcolonicb

acteria

Shinoh

arae

tal(2010)[79]

8Ap

ples

2applesday

2weeks

Platec

ount

Lactobacillus

spp

Streptococcusspp

En

terococcus

spp

Enterobacteriaceae

lecithinase-po

sitive

clostrid

iainclu

ding

Cperfr

ingens

Pseudomonas

spp

10 BioMed Research International

Table4Con

tinued

Reference

Volunteer

number

Phenolic

compo

undfood

Dose

Treatm

ent

duratio

nMicrobial

techniqu

ePo

pulatio

nincrease

Popu

latio

ndecrease

Noeffect

Tzou

nise

tal

(2011)[77]

22Cocoa

flavano

l494m

gday

29mgday

4weeks

FISH

Bifid

obacteriu

mspp

Lactobacillus

spp

Chisto

lyticum

perfringens

grou

p

Vend

ramee

tal(2011)[81]

15Wild

blueberry

drink

25gwild

blueberriesd

ay6weeks

qPCR

Bifid

obacteriu

mspp

Lacidophilus

Bacteroidesspp

Prevotellaspp

Enterococcus

spp

Ccoccoides

Queipo-

Ortun

oetal

(2012)

[78]

10Re

dwine

272m

Lday

20days

qPCR

Enterococcus

spp

Prevotellaspp

Bacteroides

Bifid

obacteriu

mspp

Bacteroidesu

niform

isEggerthella

lenta

Blautia

coccoides-E

rectaleg

roup

Clostridium

spp

Chisto

lyticum

group

Actin

obacteria

Jinetal(2012)

[75]

10Green

tea

1000

mLday

10days

T-RF

LPqP

CRBifid

obacteriu

mspp

Gug

lielm

ettiet

al(2013)[82]

15Wild

blueberries

drink

25gwild

blueberriesd

ay6weeks

qPCR

Blongum

subspinfantis

Cuervo

etal

(2014)

[86]

38

Dairy

prod

ucts

Fruits

Vegetables

Cereals

Food

intake

was

recorded

usingan

annu

alfood

frequ

ency

questio

nnaire

qPCR

Lactobacillus

Bcoccoides

Clep

tum

BioMed Research International 11

three consecutive periods After the red wine period thebacterial concentrations of proteobacteria fusobacteria Fir-micutes and Bacteroidetes markedly increased comparedwith the washout period significant increases in the num-ber of Bifidobacterium spp and Prevotella spp were alsoobserved However Lactobacillus spp Clostridium spp andC histolyticum group concentrations remained unchangedthroughout the study

In a small-scale observational study (119899 = 8) Shinoharaet al [79] found that the number of bifidobacteria in fecessignificantly increased during apple intake and the numbersof Lactobacillus spp Streptococcus spp and Enterococcusspp tended to increase On the contrary enterobacteriaand lecithinase-positive clostridia including C perfringensand Pseudomonas species tended to decrease Howeverthat study did not use culture-independent microbiologytechniques and suffered from the lack of a control groupAlso in relation to fruits another small human interventionstudy (119899 = 10) with raspberry puree [80] did not observestatistically significant alterations in the profile of colonicbacteria probably due to high interindividual variation infecal bacteria although the profiles of microbial metabolitesof raspberry polyphenols varied greatly between individualsindicating that the type of gut microbiota affects cataboliteprofiles released by bacteria in the colonThis lack of effect onthe intestinal microbiota after the intake of raspberry pureemight also be due to the short duration of the treatment aswell as the techniques employed to quantify the intestinalmicrobiota

Vendrame et al [81] studied the potential prebioticactivity of a drink elaborated fromwild blueberries especiallyrich in anthocyanins in a small intervention trial (119899 = 15) Asignificant increase in Bifidobacterium spp and L acidophilusgroup was detected while no significant differences wereobserved for Bacteroides spp Prevotella spp Enterococcusspp and C coccoides In a further paper of the same group[82] seven different intragenus bifidobacteria taxonomicclusters that were among the most common and abundantbifidobacteria species inhabiting the human gutwere targetedin the same samples It was found thatB adolescentisB breveB catenulatumpseudocatenulatum and B longum subsplongumwere always present in the group of subjects enrolledwhereas B bifidum and B longum subsp infantis were notIn spite of the large interindividual variability a significantincrease of B longum subsp infantis cell concentration wasobserved in the feces of volunteers after the wild blueberrydrink treatment which was attributed to the presence ofprebiotic (bifidogenic) molecules from blueberries possiblyfibers and glycosylated anthocyanins

In a study with postmenopausal women (119899 = 39)Clavel et al [83] found that isoflavone supplementationstimulated dominant microorganisms of the C coccoides-Erectale cluster Lactobacillus-Enterococcus group Faecalibac-terium prausnitzii subgroup and Bifidobacterium genus Itwas also suggested that the concentration of C coccoides-Erectale cluster was related to women capacity to excrete equolan intestinal metabolite from daidzein In two interventionstudies with whole grain breakfast cereals from wheat (119899 =31) and maize (119899 = 32) [84 85] the ingestion of both

products resulted in significant increases in fecal bifidobac-teria andor lactobacilli without changing the relative abun-dance of other dominant members of the gut microbiotaLittle or no changes were observed in the numbers of totalbacteria Bacteroides spp C histolyticumperfringens groupand Acetobacterium spp present in the feces However aswhole grains are good sources of dietary fiber it is difficult toascribe the observed effects only to the phenolic compoundspresent in these foods In this respect Cuervo et al [86] haverecently studied the correlations between the intake of fiberand polyphenols from diet and fecal microbiota compositionin a cohort of apparently healthy subjects Results showedthat the intake of soluble pectins and flavanones fromorangespresented a negative correlation with the levels of B coccoidesand C leptum By contrast the intake of white breadproviding hemicellulose and resistant starch was directlycorrelated with Lactobacillus

Finally another human trial (119899 = 16) carried out byJaquet et al [87] assessed the impact of a moderate con-sumption of instant coffee on the general composition ofthe human intestinal bacterial population Coffee bever-ages contain significant amounts of soluble fibre (mainlygalactomannans and arabinogalactan-proteins) and phenoliccompounds (chlorogenic acids) which arewell utilised by thehuman fecal microbiota It was observed that although fecalprofiles of the dominant microbiota were not significantlyaffected after the consumption of the coffee the populationof Bifidobacterium spp increased being the largest increaseobserved for those volunteers showing the lowest initialbifidobacteria levels

8 Conclusions

This review has tried to summarize the current knowledgein relation to the phenolic metabolism by gut microbiota andthemodulation of the gutmicrobiota by phenolic compoundsand polyphenol-rich dietary sourcesThere are evidences thatthe beneficial effects attribute to dietary polyphenols dependon their biotransformation by the gut microbiota Thereforeit is important to investigate the bacterial species impli-cated in the metabolism of dietary polyphenols and furtherresearch is still needed in relation to the resultant microbialmetabolites to ascertain their mechanisms of action Onthe other hand a great number of in vitro and in vivo (inanimals andhumans) studies showing the influence of dietarypolyphenols on gut-inhabiting bacteria have been publishedin recent years Although in vitro assays facilitate experimen-tation caution must be taken in extrapolating results to invivo situation as many factors are acting upon this processIn general in both in vitro and in vivo studies polyphenols orpolyphenol-rich sources have shown to influence the relativeabundance of different bacterial groups within the gut micro-biota reducing numbers of potential pathogens including Cperfringens and C histolyticum and certain Gram-negativeBacteroides spp and enhancing mainly beneficial Clostridiabifidobacteria and lactobacilli A better understanding of theinteraction between dietary polyphenols and gut microbiotathrough the emerging advances in high-throughput meta-genomic transcriptomic and proteomic approaches would

12 BioMed Research International

be essential in order to identify genes and micro-organismsinvolved in polyphenol (in)activation and conversion andthus to elucidate the implications of diet on the modulationof microbiota for delivering health benefits

Functional foods are considered to enhance the protectiveeffects against diseases derived from some food componentsIn the last decades dairy fermented foods have probablybeen one of the most-developed functional products andhave deserved intensive research In this expansion dairyfermented foods have been supplemented with fruits cerealsand other stuffs of plant origin all of which represent a highpercentage of the current market of the dairy industry Theseproducts have a healthy appeal which attracts consumersThus fruit juicesconcentrates and prepared fruits (in theform of pieces pulp and even flour) have been successfullyincorporated in dairy fermented foods as sources of prebioticfibers and phytochemicals Among these phytochemicalspresent in plant-derived foods polyphenols have gainedmuch interest due to their diverse potential beneficial effectsin human health The supplementation of dairy fermentedproducts with rich-polyphenolic stuffs (phenolic extractsphenolic-enriched fractions etc) seems to be an effectivetechnological option to improve the benefits of these productsin the balance of the intestinal microbiota due not only to theaction of the probiotics but also to the potential modulationeffects exerted by polyphenols as it has been described in thisreview Further research in this area will aim to accomplishthe benefits of both probiotic strains and polyphenols inrelation to gut health

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors of this review were funded by the SpanishMINECO through different projects (AGL2012-40172-C02-01 AGL2010-17499 and BFU2012-35228) and the CON-SOLIDER INGENIO 2010 programme (project FUN-C-FOOD CSD2007-063) as well as Comunidad de Madrid(project ALIBIRD P2009AGR-1469) Montserrat Duenaswould like to thank the Spanish ldquoRamon y Cajalrdquo Programmefor a contract

References

[1] S E Power P W OrsquoToole C Stanton R P Ross and GF Fitzgerald ldquoIntestinal microbiota diet and healthrdquo BritishJournal of Nutrition vol 111 no 3 pp 387ndash402 2014

[2] PDeCruz L Prideaux JWagner et al ldquoCharacterization of thegastrointestinal microbiota in health and inflammatory boweldiseaserdquo Inflammatory Bowel Diseases vol 18 no 2 pp 372ndash390 2012

[3] A Kramer S Bekeschus B M Broker H Schleibinger BRazavi and O Assadian ldquoMaintaining health by balancingmicrobial exposure and prevention of infection the hygienehypothesis versus the hypothesis of early immune challengerdquoJournal of Hospital Infection vol 83 no 1 pp S29ndashS34 2013

[4] M Rescigno ldquoIntestinal microbiota and its effects on theimmune systemrdquo Cellular Microbiology vol 16 no 7 pp 1004ndash1013 2014

[5] M G L Hertog E J M Feskens P C H HollmanM B Katanand D Kromhout ldquoDietary antioxidant flavonoids and risk ofcoronary heart disease the Zutphen Elderly StudyrdquoThe Lancetvol 342 no 8878 pp 1007ndash1011 1993

[6] I C W Arts and P C H Hollman ldquoPolyphenols and diseaserisk in epidemiologic studiesrdquoThe American Journal of ClinicalNutrition vol 81 no 1 pp 317Sndash325S 2009

[7] D del Rio A Rodriguez-Mateos J P E Spencer M TognoliniG Borges and A Crozier ldquoDietary (poly)phenolics in humanhealth structures bioavailability and evidence of protectiveeffects against chronic diseasesrdquo Antioxidants amp Redox Signal-ing vol 18 no 14 pp 1818ndash1892 2013

[8] F Perez-Vizcaino and J Duarte ldquoFlavonols and cardiovasculardiseaserdquo Molecular Aspects of Medicine vol 31 no 6 pp 478ndash494 2010

[9] J P E Spencer K Vafeiadou R J Williams and D VauzourldquoNeuroinflammation modulation by flavonoids and mecha-nisms of actionrdquo Molecular Aspects of Medicine vol 33 no 1pp 83ndash97 2012

[10] J M Laparra and Y Sanz ldquoInteractions of gut microbiota withfunctional food components and nutraceuticalsrdquo Pharmacolog-ical Research vol 61 no 3 pp 219ndash225 2010

[11] X He M L Marco and C M Slupsky ldquoEmerging aspects offood and nutrition on gut microbiotardquo Journal of Agriculturaland Food Chemistry vol 61 no 40 pp 9559ndash9574 2013

[12] D Hervert-Hernandez and I Goni ldquoDietary polyphenols andhuman gut microbiota a reviewrdquo Food Reviews Internationalvol 27 no 2 pp 154ndash169 2011

[13] K M Tuohy L Conterno M Gasperotti and R Viola ldquoUp-regulating the human intestinal microbiome using whole plantfoods polyphenols andor fiberrdquo Journal of Agricultural andFood Chemistry vol 60 no 36 pp 8776ndash8782 2012

[14] U Etxeberria A Fernandez-Quintela F I Milagro L AguirreJ A Martınez and M P Portillo ldquoImpact of polyphenols andpolyphenol-rich dietary sources on gut microbiota composi-tionrdquo Journal of Agricultural and Food Chemistry vol 61 no 40pp 9517ndash9533 2013

[15] F Cardona C Andres-Lacueva S Tulipani F J Tinahonesand M I Queipo-Ortuno ldquoBenefits of polyphenols on gutmicrobiota and implications in human healthrdquo Journal ofNutritional Biochemistry vol 24 no 8 pp 1415ndash1422 2013

[16] M V Selma J C Espın and F A Tomas-Barberan ldquoInteractionbetween phenolics and gut microbiota role in human healthrdquoJournal of Agricultural and Food Chemistry vol 57 no 15 pp6485ndash6501 2009

[17] T RequenaMMonagasM A Pozo-Bayon et al ldquoPerspectivesof the potential implications ofwine polyphenols on humanoraland gut microbiotardquo Trends in Food Science amp Technology vol21 no 7 pp 332ndash344 2010

[18] J Van Duynhoven E E Vaughan F van Dorsten et alldquoInteractions of black tea polyphenols with human gut micro-biota implications for gut and cardiovascular health1-4rdquo TheAmerican Journal of Clinical Nutrition vol 98 no 6 pp 1631Sndash1641S 2013

[19] SMoco F-P JMartin and S Rezzi ldquoMetabolomics view on gutmicrobiome modulation by polyphenol-rich foodsrdquo Journal ofProteome Research vol 11 no 10 pp 4781ndash4790 2012

BioMed Research International 13

[20] R K Buddington and P T Sangild ldquoCompanion animalssymposium development of the mammalian gastrointestinaltract the resident microbiota and the role of diet in early liferdquoJournal of Animal Science vol 89 no 5 pp 1506ndash1519 2011

[21] K Tiihonen A C Ouwehand and N Rautonen ldquoHumanintestinal microbiota and healthy ageingrdquo Ageing ResearchReviews vol 9 no 2 pp 107ndash116 2010

[22] D Mariat O Firmesse F Levenez et al ldquoThe firmicutesbacteroidetes ratio of the human microbiota changes with agerdquoBMCMicrobiology vol 9 article 123 2009

[23] M Arumugam J Raes E Pelletier et al ldquoEnterotypes of thehuman gutmicrobiomerdquoNature vol 473 no 7346 pp 174ndash1802011

[24] G D Wu J Chen C Hoffmann et al ldquoLinking long-termdietary patterns with gut microbial enterotypesrdquo Science vol334 no 6052 pp 105ndash108 2011

[25] I B JefferyM J Claesson PWOrsquoToole and F Shanahan ldquoCat-egorization of the gut microbiota enterotypes or gradientsrdquoNature Reviews Microbiology vol 10 no 9 pp 591ndash592 2012

[26] WM de Vos andM Nieuwdorp ldquoGenomics a gut predictionrdquoNature vol 498 no 7452 pp 48ndash49 2013

[27] P B Eckburg E M Bik C N Bernstein et al ldquoMicrobiologydiversity of the human intestinal microbial florardquo Science vol308 no 5728 pp 1635ndash1638 2005

[28] E G Zoetendal C T Collier S Koike R I Mackie and H RGaskins ldquoMolecular ecological analysis of the gastrointestinalmicrobiota a reviewrdquo Journal of Nutrition vol 134 no 2 pp465ndash472 2004

[29] M H Fraher PW OrsquoToole and E MM Quigley ldquoTechniquesused to characterize the gut microbiota a guide for the clini-cianrdquo Nature Reviews Gastroenterology and Hepatology vol 9no 6 pp 312ndash322 2012

[30] R A Kemperman S Bolca L C Roger and E E VaughanldquoNovel approaches for analysing gut microbes and dietarypolyphenols challenges and opportunitiesrdquo Microbiology vol156 no 11 pp 3224ndash3231 2010

[31] R A Kemperman G Gross S Mondot et al ldquoImpact ofpolyphenols from black tea and red winegrape juice on a gutmodel microbiomerdquo Food Research International vol 53 no 2pp 659ndash669 2013

[32] M N Clifford ldquoDiet-derived phenols in plasma and tissues andtheir implications for healthrdquo Planta Medica vol 70 no 12 pp1103ndash1114 2004

[33] A Crozier D del Rio and M N Clifford ldquoBioavailability ofdietary flavonoids and phenolic compoundsrdquoMolecular Aspectsof Medicine vol 31 no 6 pp 446ndash467 2010

[34] A J Day M S Dupont S Ridley et al ldquoDeglycosylation offlavonoid and isoflavonoid glycosides by human small intestineand liver beta-glucosidase activityrdquo FEBS Letters vol 436 no 1pp 71ndash75 1998

[35] A J Day F J Canada J C Dıaz et al ldquoDietary flavonoid andisoflavone glycosides are hydrolysed by the lactase site of lactasephlorizin hydrolaserdquo FEBS Letters vol 468 no 2-3 pp 166ndash1702000

[36] A Scalbert and G Williamson ldquoDietary intake and bioavail-ability of polyphenolsrdquo Journal of Nutrition vol 130 no 8 pp2073Sndash2085S 2000

[37] A R Rechner G Kuhnle H Hu et al ldquoThe metabolism ofdietary polyphenols and the relevance to circulating levels ofconjugated metabolitesrdquo Free Radical Research vol 36 no 11pp 1229ndash1241 2002

[38] A-M Aura K A OrsquoLeary G Williamson et al ldquoQuercetinderivatives are deconjugated and converted to hydroxypheny-lacetic acids but not methylated by human fecal flora in vitrordquoJournal of Agricultural and Food Chemistry vol 50 no 6 pp1725ndash1730 2002

[39] A-M Aura ldquoMicrobial metabolism of dietary phenolic com-pounds in the colonrdquo Phytochemistry Reviews vol 7 no 3 pp407ndash429 2008

[40] M Monagas M Urpi-Sarda F Sanchez-Patan et al ldquoInsightsinto themetabolism andmicrobial biotransformation of dietaryflavan-3-ols and the bioactivity of their metabolitesrdquo Food andFunction vol 1 no 3 pp 233ndash253 2010

[41] GWilliamson andMNClifford ldquoColonicmetabolites of berrypolyphenols the missing link to biological activityrdquo BritishJournal of Nutrition vol 104 no 3 pp S48ndashS66 2010

[42] D M Jacobs E Gaudier J van Duynhoven and E E VaughanldquoNon-digestible food ingredients colonic microbiota and theimpact on gut health and immunity a role for metabolomicsrdquoCurrent Drug Metabolism vol 10 no 1 pp 41ndash54 2009

[43] S Bolca S Possemiers V Maervoet et al ldquoMicrobial anddietary factors associatedwith the 8-prenylnaringenin producerphenotype a dietary intervention trial with fifty healthy post-menopausal Caucasian womenrdquo British Journal of Nutritionvol 98 no 5 pp 950ndash959 2007

[44] X Tzounis J Vulevic G G C Kuhnle et al ldquoFlavanolmonomer-induced changes to the human faecal microflorardquoBritish Journal of Nutrition vol 99 no 4 pp 782ndash792 2008

[45] M Hidalgo M J Oruna-Concha S Kolida et al ldquoMetabolismof anthocyanins by human gut microflora and their influenceon gut bacterial growthrdquo Journal of Agricultural and FoodChemistry vol 60 no 15 pp 3882ndash3890 2012

[46] A L Molan M A Lila J Mawson and S De ldquoIn vitroand in vivo evaluation of the prebiotic activity of water-soluble blueberry extractsrdquo World Journal of Microbiology andBiotechnology vol 25 no 7 pp 1243ndash1249 2009

[47] D Bialonska P Ramnani S G Kasimsetty K R Muntha GR Gibson and D Ferreira ldquoThe influence of pomegranate by-product and punicalagins on selected groups of human intesti-nal microbiotardquo International Journal of FoodMicrobiology vol140 no 2-3 pp 175ndash182 2010

[48] G Mandalari R M Faulks C Bisignano K W Waldron ANarbad and M S J Wickham ldquoIn vitro evaluation of theprebiotic properties of almond skins (Amygdalus communisL)rdquoFEMS Microbiology Letters vol 304 no 2 pp 116ndash122 2010

[49] V Fogliano M L Corollaro P Vitaglione et al ldquoIn vitro bioac-cessibility and gut biotransformation of polyphenols present inthe water-insoluble cocoa fractionrdquoMolecular Nutritionamp FoodResearch vol 55 supplement 1 pp S44ndashS55 2011

[50] M J Pozuelo A Agis-Torres D Hervert-Hernandez etal ldquoGrape antioxidant dietary fiber stimulates Lactobacillusgrowth in rat cecumrdquo Journal of Food Science vol 77 no 2 ppH59ndashH62 2012

[51] C Cueva F Sanchez-Patan M Monagas et al ldquoIn vitrofermentation of grape seed flavan-3-ol fractions by humanfaecal microbiota changes in microbial groups and phenolicmetabolitesrdquo FEMSMicrobiology Ecology vol 83 no 3 pp 792ndash805 2013

[52] F Sanchez-Patan C CuevaMMonagas et al ldquoIn vitro fermen-tation of a red wine extract by human gut microbiota changesin microbial groups and formation of phenolic metabolitesrdquoJournal of Agricultural and Food Chemistry vol 60 no 9 pp2136ndash2147 2012

14 BioMed Research International

[53] E Barroso F Sanchez-Patan P J Martın-Alvarez et al ldquoLacto-bacillus plantarum IFPL935 favors the initial metabolism of redwine polyphenols when added to a colonic microbiotardquo Journalof Agricultural and Food Chemistry vol 61 no 42 pp 10163ndash10172 2013

[54] G R Gibson J H Cummings and G T Macfarlane ldquoUse ofa three-stage continuous culture system to study the effect ofmucin on dissimilatory sulfate reduction and methanogenesisby mixed populations of human gut bacteriardquo Applied andEnvironmentalMicrobiology vol 54 no 11 pp 2750ndash2755 1988

[55] KMollyMVandeWoestyne andWVerstraete ldquoDevelopmentof a 5-step multi-chamber reactor as a simulation of thehuman intestinal microbial ecosystemrdquo Applied Microbiologyand Biotechnology vol 39 no 2 pp 254ndash258 1993

[56] M Minekus M Smeets-Peeters A Bernalier et al ldquoAcomputer-controlled system to simulate conditions of thelarge intestine with peristaltic mixing water absorption andabsorption of fermentation productsrdquoAppliedMicrobiology andBiotechnology vol 53 no 1 pp 108ndash114 1999

[57] PDeBoever BDeplancke andWVerstraete ldquoFermentation bygut microbiota cultured in a simulator of the human intestinalmicrobial ecosystem is improved by supplementing a soygermpowderrdquo Journal of Nutrition vol 130 no 10 pp 2599ndash26062000

[58] C S Yang X Wang G Lu and S C Picinich ldquoCancerprevention by tea animal studies molecular mechanisms andhuman relevancerdquoNature Reviews Cancer vol 9 no 6 pp 429ndash439 2009

[59] R E Ley F Backhed P Turnbaugh C A Lozupone R DKnight and J I Gordon ldquoObesity alters gut microbial ecologyrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 102 no 31 pp 11070ndash11075 2005

[60] H Hara N Orita S Hatano et al ldquoEffect of tea polyphenols onfecal flora and fecal metabolic products of pigsrdquo The Journal ofVeterinary Medical Science vol 57 no 1 pp 45ndash49 1995

[61] N Ishihara D-C Chu S Akachi and L R Juneja ldquoImprove-ment of intestinal microflora balance and prevention of diges-tive and respiratory organ diseases in calves by green teaextractsrdquo Livestock Production Science vol 68 no 2-3 pp 217ndash229 2001

[62] P Dolara C Luceri C De Filippo et al ldquoRed wine polyphenolsinfluence carcinogenesis intestinal microflora oxidative dam-age and gene expression profiles of colonicmucosa in F344 ratsrdquoMutation Research-Fundamental and Molecular Mechanisms ofMutagenesis vol 591 no 1-2 pp 237ndash246 2005

[63] S Sembries G Dongowski K Mehrlander F Will and HDietrich ldquoPhysiological effects of extraction juices from applegrape and red beet pomaces in ratsrdquo Journal of Agricultural andFood Chemistry vol 54 no 26 pp 10269ndash10280 2006

[64] S Sembries G Dongowski G Jacobasch K Mehrlander FWill andH Dietrich ldquoEffects of dietary fibre-rich juice colloidsfrom apple pomace extraction juices on intestinal fermentationproducts and microbiota in ratsrdquo British Journal of Nutritionvol 90 no 3 pp 607ndash615 2003

[65] A Viveros S Chamorro M Pizarro I Arija C Centeno andA Brenes ldquoEffects of dietary polyphenol-rich grape productson intestinal microflora and gut morphology in broiler chicksrdquoPoultry Science vol 90 no 3 pp 566ndash578 2011

[66] A H Smith and R I Mackie ldquoEffect of condensed tannins onbacterial diversity andmetabolic activity in the rat gastrointesti-nal tractrdquo Applied and Environmental Microbiology vol 70 no2 pp 1104ndash1115 2004

[67] M Massot-Cladera T Perez-Berezo A Franch M Castelland F J Perez-Cano ldquoCocoa modulatory effect on rat faecalmicrobiota and colonic crosstalkrdquo Archives of Biochemistry andBiophysics vol 527 no 2 pp 105ndash112 2012

[68] M Larrosa M J Yanez-Gascon M V Selma et al ldquoEffectof a low dose of dietary resveratrol on colon microbiotainflammation and tissue damage in a DSS-induced colitis ratmodelrdquo Journal of Agricultural and Food Chemistry vol 57 no6 pp 2211ndash2220 2009

[69] A-L Molan Z Liu andM Kruger ldquoThe ability of blackcurrantextracts to positively modulate key markers of gastrointestinalfunction in ratsrdquoWorld Journal ofMicrobiologyampBiotechnologyvol 26 no 10 pp 1735ndash1743 2010

[70] A Lacombe R W Li D Klimis-Zacas et al ldquoLowbush wildblueberries have the potential to modify gut microbiota andxenobiotic metabolism in the rat colonrdquo PLoS ONE vol 8 no6 Article ID e67497 2013

[71] R Saad M R Rizkallah and R K Aziz ldquoGut Pharmacomicro-biomics the tip of an iceberg of complex interactions betweendrugs and gut-associated microbesrdquo Gut Pathogens vol 4 no1 article 16 2012

[72] E J J Van Velzen J A Westerhuis J P M van Duynhovenet al ldquoMultilevel data analysis of a crossover designed humannutritional intervention studyrdquo Journal of Proteome Researchvol 7 no 10 pp 4483ndash4491 2008

[73] T Okubo N Ishihara H Takahashi et al ldquoEffects of partiallyhydrolyzed guar gum intake on human intestinal microfloraand itsmetabolismrdquoBioscience Biotechnology andBiochemistryvol 58 no 8 pp 1364ndash1369 1994

[74] V Mai H A Katki H Harmsen et al ldquoEffects of a controlleddiet and black tea drinking on the fecalmicroflora compositionand the fecal bile acid profile of human volunteers in a double-blinded ramdomized feeding studyrdquo The Journal of Nutritionvol 134 no 2 pp 473ndash478 2004

[75] J-S Jin M Touyama T Hisada and Y Benno ldquoEffectsof green tea consumption on human fecal microbiota withspecial reference to Bifidobacterium speciesrdquoMicrobiology andImmunology vol 56 no 11 pp 729ndash739 2012

[76] J Yamakoshi S Tokutake M Kikuchi Y Kubota H Konishiand T Mitsuoka ldquoEffect of proantocyanidin -rich extract fromgrape seed on human fecal flora and fecalodorrdquo FASEB Journalvol 15 no 4 p A633 2001

[77] X Tzounis A Rodriguez-Mateos J Vulevic G R Gibson CKwik-Uribe and J P E Spencer ldquoPrebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomizedcontrolled double-blind crossover intervention studyrdquo TheAmerican Journal of Clinical Nutrition vol 93 no 1 pp 62ndash722011

[78] M I Queipo-Ortuno M Boto-Ordonez M Murri et alldquoInfluence of red wine polyphenols and ethanol on the gutmicrobiota ecology and biochemical biomarkersrdquo AmericanJournal of Clinical Nutrition vol 95 no 6 pp 1323ndash1334 2012

[79] K Shinohara Y Ohashi K Kawasumi A Terada and TFujisawa ldquoEffect of apple intake on fecal microbiota andmetabolites in humansrdquo Anaerobe vol 16 no 5 pp 510ndash5152010

[80] C I R Gill G J Mcdougall S Glidewell et al ldquoProfiling ofphenols in human fecal water after raspberry supplementationrdquoJournal of Agricultural and Food Chemistry vol 58 no 19 pp10389ndash10395 2010

[81] S Vendrame S Guglielmetti P Riso S Arioli D Klimis-Zacasand M Porrini ldquoSix-week consumption of a wild blueberry

BioMed Research International 15

powder drink increases Bifidobacteria in the human gutrdquoJournal of Agricultural and Food Chemistry vol 59 no 24 pp12815ndash12820 2011

[82] S Guglielmetti D Fracassetti V Taverniti et al ldquoDifferentialmodulation of human intestinal Bifidobacterium populationsafter consumption of a wild blueberry (Vaccinium angusti-folium) drinkrdquo Journal of Agricultural and Food Chemistry vol61 no 34 pp 8134ndash8140 2013

[83] T Clavel M Fallani P Lepage et al ldquoIsoflavones and func-tional foods alter the dominant intestinal microbiota in post-menopausal womenrdquo Journal of Nutrition vol 135 no 12 pp2786ndash2792 2005

[84] A Costabile A Klinder F Fava et al ldquoWhole-grain wheatbreakfast cereal has a prebiotic effect on the human gut micro-biota a double-blind placebo-controlled crossover studyrdquoBritish Journal of Nutrition vol 99 no 1 pp 110ndash120 2008

[85] A L Carvalho-Wells K Helmolz C Nodet et al ldquoDetermina-tion of the in vivo prebiotic potential of a maize-based wholegrain breakfast cereal a human feeding studyrdquo British Journalof Nutrition vol 104 no 9 pp 1353ndash1356 2010

[86] A Cuervo L Valdes N Salazar et al ldquoPilot study of diet andmicrobiota interactive associations of fibers and polyphenolswith human intestinal bacteriardquo Journal of Agricultural andFood Chemistry vol 62 no 23 pp 5330ndash5336 2014

[87] M Jaquet I Rochat J Moulin C Cavin and R BibilonildquoImpact of coffee consumption on the gut microbiota a humanvolunteer studyrdquo International Journal of FoodMicrobiology vol130 no 2 pp 117ndash121 2009

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Page 4: Review Article A Survey of Modulation of Gut Microbiota by ...downloads.hindawi.com/journals/bmri/2015/850902.pdf · Review Article A Survey of Modulation of Gut Microbiota by Dietary

4 BioMed Research International

as obtained from different methodological approaches andmicrobial analysis techniques

4 Studies Using Batch Culture Fermentations

Although in vivo human or animal intervention trials arephysiologically most relevant to study both polyphenolmetabolism and microbial modulation in vitro tools havebeen designed to simulate intestinal conditions In combi-nation with in vivo trials in vitro experiments may help toelucidate the extent bioconversion processes mediated by thehost itself [42 43] The complexity of in vitro gut models isdiverse ranging from simple static models (batch culture fer-mentation) to advanced continuous models (gastrointestinalsimulators)

Simple static gut models also known as batch-typecultures are generally closed systems using sealed bottlesor reactors containing suspensions of fecal material that aremaintained under anaerobic conditions They are relativelyeasy to operate and cost-effective have a fair throughputand allow for parallel screening This model approach isprimarily used to assess the stability of polyphenols in thepresence of human-derived gut microbiota and to evaluatewhich environmental conditions favor or limit polyphenolbioconversion However these static gut models are onlyadequate for simulating short-term conditions in the gutfor assessment of long-term adaptations of the gut microbialcommunity more complex dynamic models are needed[12]

Table 1 reports different studies of modulation of gutmicrobiota by dietary polyphenols using batch-type culturesDetails about fermentation conditions (fecal concentrationpolyphenol origin and dose and incubation time) andmicro-bial techniques used and main effects on bacteria groups(growth enhancement growth inhibition or no effect) havebeen included As general characteristics fecal fermentationsemployed feces concentration le10 (wv) and lasted 48 hmaximum Both pure phenolic compounds and phenolic-rich extracts were added to the fecal medium at a finalconcentration lt10 (wv) and changes in specific bacterialgroups weremainly assessed by FISH analysis A first relevantexperiment using batch culture fermentation was carriedout by Tzounis et al [44] who found that the flavan-3-olmonomers [(minus)-epicatechin and (+)-catechin] promoted thegrowth of Clostridium coccoides-Eubacterium rectale groupwhich is known to produce large amounts of butyrate a short-chain fatty acid (SCFA) with anti-inflammatory and anti-neoplasic properties (+)-catechin also increased the growthof Lactobacillus-Enterococcus spp Bifidobacterium spp andEscherichia coli but decreased the growth of Clostridiumhistolyticum Also using standard compounds Hidalgo et al[45] found that anthocyanins (ie malvidin-3-glucoside andamixture of anthocyanins) significantly enhanced the growthof Lactobacillus-Enterococcus spp and Bifidobacterium sppIn addition malvidin-3-glucoside showed a tendency topromote the growth of the C coccoides-E rectale group

Similar results have been observed in batch culturefermentations with phenolic-rich extracts from different

sourcesMolan et al [46] found that the addition of blueberryextracts to a mixture of fecal bacterial populations signifi-cantly increased the number of lactobacilli and bifidobacteria(Table 1) In the same line Bialonska et al [47] reportedenhancement of the growth of total bacteria Bifidobacteriumspp and Lactobacillus-Enterococcus spp in response to acommercial extract of pomegranate without influencing theC coccoides-E rectale and C histolyticum groups (Table 1)Mandalari et al [48] suggested a potential prebiotic effectfor natural and blanched almond skins as these foodstuffs infermentations with fecal microbiota significantly increasedthe populations of bifidobacteria and C coccoides-E rectalegroup and decreased the number of C hystolyticum groupThese authors related the possible prebiotic effect by almondskins not only to a high amount of dietary fibre but also tosome phenolic compounds such as ferulic acid flavan-3-olsand flavonols present in the almond skins [48] Fogliano et al[49] carried out an in vitro fermentation with a water-insoluble cocoa fraction in a three-stage continuous culturecolonicmodel system It was observed that this cocoa fractionpresented prebiotic activity producing a significant increasein lactobacilli and bifidobacteria as well as an increase inbutyrate production They concluded that the coexistenceof fermentable polysaccharides and free flavanol monomersin cocoa such as catechins might be very effective in themodification of gut microbiota Similar conclusions weredrawn by Pozuelo et al [50] who found a significant increaseof the growth of Lactobacillus reuteri and Lactobacillusacidophilus in the presence of a grape antioxidant dietary fibernaturally obtained from red grapes Our research group car-ried out several batch culture fermentations of two flavan-3-ol fractions with different degree of polymerisation and winepolyphenols with fecal microbiota from different healthyvolunteers [51 52] Both flavan-3-ol fractions promoted thegrowth ofLactobacillusEnterococcus spp and inhibited theChistolyticum group during fermentation although the effectswere only statistically significant with the less polymerizedfractionWine polyphenols only showed a slight inhibition intheC histolyticum group probably due to their lower contentin flavan-3-ols

Additionally this type of fermentations has also beenused to assess the contribution of certain probiotic strainsto the colonic metabolism of polyphenols In this senseBarroso et al [53] carried out fermentations of a red wineextract inoculated with human microbiota obtained fromthe colonic compartments of a dynamic simulator in thepresence and absence of the probiotic strain L plantarumIFPL935 Microbial analysis by qPCR indicated that redwine polyphenols induced greater variations among in vitrobatches harboring different colon-region (ascending colondescending colon and effluent) microbiota than those foundwhen L plantarum IFPL935 was added Batches inoculatedwith microbiota from the ascending colon were shown toharbor the major proportion of saccharolytic bacteria (Bac-teroides Bifidobacterium and Prevotella) whereas Clostrid-ium groups were found in major numbers in the batchesinoculated with microbiota simulating the distal regions [53](Table 1)

BioMed Research International 5

Table1Stud

iesu

singbatchcultu

referm

entatio

n

Reference

Fecal

concentration

Phenolic

compo

undfood

Dose

Timeo

fincubatio

nMicrobial

techniqu

eGrowth

enhancem

ent

Growth

inhibitio

nNoeffect

Tzou

nise

tal

(2008)

[44]

10w

v(+)-catechin

150m

gL

1000

mgL

lt48

hFISH

Lactobacillus-

Enterococcus

spp

Bifid

obacteriu

mspp

Ccoccoides-E

rectale

grou

pE

coli

Chisto

lyticum

grou

p

Molan

etal(2009)

[46]

01

vv

Blueberryextracts

510

and25

48h

FISH

Lactob

acilli

Bifid

obacteria

Bialon

skae

tal

(2010)

[47]

10w

vPo

megranate

extractand

punicalagin

10

48h

FISH

Totalbacteria

Bifid

obacteriu

mspp

Lactobacillus-

Enterococcus

spp

Ccoccoides-E

rectale

grou

pC

histo

lyticum

grou

p

Mandalarietal

(2010)

[48]

10w

vAlm

ondskins

1w

vpredigested

almon

dskins

lt24

hFISH

Bifid

obacteria

Ccoccoides-E

rectale

grou

p

Chisto

lyticum

grou

p

Fogliano

etal

(2011)[49]

5w

vWater-in

soluble

cocoafraction

1w

v36

hFISH

Bifid

obacteria

Lactob

acilli

Cuevae

tal(2013)

[51]

10w

vGrape

seed

extract

fractio

ns300ndash

450m

gL

lt48

hFISH

Lactobacillus-

Enterococcus

spp

Chisto

lyticum

grou

p

Hidalgo

etal

(2012)

[45]

10w

v

Malvidin-3-O-

glucoside

Antho

cyanidins

mixture

20mgLand

200m

gL

4850

mgLand

48500m

gL

lt24

hFISH

Lactobacillus-

Enterococcus

spp

Bifid

obacteriu

mspp

Ccoccoides-E

rectale

grou

p

Sanchez-Patanet

al(2012)[52]

1wv

Redwinee

xtract

600m

gL

48h

FISH

Chisto

lyticum

grou

p

Lactobacillus-

Enterococcus

spp

Barrosoetal

(2013)

[53]

Redwinee

xtract

500m

gL

48h

qPCR

Lactobacillus

spp

Bifid

obacteriu

mspp

Bacteroidesspp

Ru

minococcusspp

6 BioMed Research International

Table 2 Studies using the gastrointestinal simulators (ie SHIME)

Reference Simulator Phenoliccompoundfood Dose Time Microbial

techniquePopulationincrease Population decrease

De Boeveret al (2000)[57]

SHIME Soy germ powder 25 gday 2 weeks Plate count

EnterobacteriaceaeColiforms

Lactobacillus sppStaphylococcus sppClostridium spp

Kempermanet al (2013)[31]

Twin-SHIME Black tea extract

3 times dailydosing(1000mg

polyphenolsas total daily

dose)

2 weeks

Plate countqPCR

PCR-DGGEpyrosequencing

Klebsiella sppEnterococci

Akkermansia spp

BifidobacteriaBlautia coccoidesAnaeroglobus sppVictivallis spp

Kempermanet al (2013)[31]

Twin-SHIME

Red wine-grapeextract

3 times dailydosing(1000mg

polyphenolsas total daily

dose)

2 weeks

Plate countqPCR

PCR-DGGEpyrosequencing

Klebsiella sppAlistipes spp

Cloacibacillus sppVictivallis spp

Akkermansia spp

BifidobacteriaBlautia coccoides

groupAnaeroglobus spp

Subdoligranulum sppBacteroides

5 Studies Using HumanGastrointestinal Simulators

In contrast to short-duration experiments with static gutmodels longer-term experiments are required when theadaptation of the gut microbial community to dietarypolyphenols needs to be assessed To this end dynamic invitro gut models such as the ldquoReadingrdquo model [54] theSimulator of the Human Intestinal Microbial Ecosystem(SHIME) the TNO Intestinal Model 2 (TIM2) [55 56] andthe recent gastrointestinal simulator set up in our Institute(SIMGI) (unpublished work) have been developed where gutmicrobiota are cultured over a longer time frame (days toweeks) in one or multiple connected pH controlled vesselsrepresenting different parts of the gastrointestinal tract

As an example of the versatility and potential of humangastrointestinal simulators Table 2 reports a series of studiesabout modulation of gut microbiota by polyphenols usingthe SHIME [57 58]This validatedmodel comprises stomachand small intestinal sections for predigestion of food aswell as vessels stimulating the ascending transcending anddescending parts of the human colon allowing assessment ofchanges in the different colonic areas that are very challengingto access in a human intervention However it should beunderlined that this approach takes for granted that theextracts reach intact the colonic region and no nutrientabsorption is consideredThe use of the SHIME to investigatethe effects of a soy germ powder on the fermentative capacityof the simulated microbiota of the colon was the aim of astudy carried out by De Boever et al [57]They observed thatthe addition of the soy germ powder in a 2-week treatmentresulted into an overall increase of bacterial marker pop-ulations (Enterobacteriaceae coliforms Lactobacillus sppStaphylococcus spp and Clostridium spp) with a significantincrease of 2 log10 units in the Lactobacillus spp populationMore recently Kemperman et al [31] using the twin-SHIME

model studied the influence of a bolus dose and a 2-weekcontinuous administration of complex dietary polyphenolsfrom black tea or red wine grape extracts on the colonicmicrobiota The Twin-SHIME system involving two modelsthat run in parallel was inoculatedwith the same fecal samplefor direct comparison of the effect of the two polyphenoltypes A combination of analyses including cultivation PCR-denaturing gradient gel electrophoresis (DGGE) quantita-tive PCR and high throughput pyrosequencing of the 16Sribosomal RNA gene was applied to characterize micro-bial community changes This study showed that complexpolyphenols in the context of a model system can modulateselect members of the human gut microbiota revealing noveltargets potentially involved in polyphenolmetabolism andorresistant microbes to be further investigated for polyphenolmetabolism or resistance mechanisms [31]

6 Animal Models Studies

It is widely assumed that preliminary evidence should bewarranted in animal models before human interventiontrials Animal models contribute to better understanding themechanisms and biological effects that could be likely tohappen in the human body The metabolism of polyphenolshas been object of numerous animal studies (mostly inrodents) especially for their impact on metabolic disorders[58] but only a few of these studies have followed thedynamics and composition of the intestinal microbiota inassociation with polyphenol metabolites retrieved from thehost Caution is required in extrapolating results to humansbecause culture-independent comparisons have revealed thatmost bacterial genera and species found in mice are not seenin humans although the distal gut microbiota of mice andhumans harbors the same bacterial phyla [59] In this sectionstudies performed in animals in order to assess the effects ofpolyphenols on the modulation of intestinal microbiota are

BioMed Research International 7

Table 3 Animal model studies

Reference Animal Phenoliccompoundfood Dose Treatment

durationMicrobialtechnique Population increase Population decrease

Hara et al(1995) [60] Pigs Tea polyphenols 02 (free access) 2 weeks Plate count Lactobacilli

Total bacteriaBacteroidaceaeC perfringens

Ishihara et al(2001) [61] Calves Green tea extracts 15 gday 4 weeks Plate count

Bifidobacterium sppLactobacillus sppC perfringens

Smith andMackie (2004)[66]

Rats

Proantocyanidinsextracted from

Acaciaangustissima

07 (low tannindiet) and 20

(high tannin diet)

35 weekstreatment +35 weekswashout

PCR-DGGEDot blot

hybridization

Bacteroides fragilisgroup

Bacteroides-Prevotella-

Porphyromonas group

Enterobacteriaceae

C leptum group

Dolara et al(2005) [62] Rats

Red winepolyphenolspowder

50mgkg 16 weeks Plate count LactobacilliBifidobacteria

PropionibacteriaBacteroidesClostridia

Sembries et al(2006) [63] Rats Apple juice free access 4 weeks Plate count Lactobacilli

BifidobacteriaSembries et al(2003) [64] Rats Apple pomace

juice colloid5 suppl diet(free access) 6 weeks Plate count

FISH Bacteroidaceae

Larrosa et al(2009) [68] Rats Resveratrol 1mgkgday 25 days Plate count Lactobacilli

Bifidobacteria

Molan et al(2010) [69] Rats

Blackcurrantextracts (leaf or

berry)

3 timesweek(i) 30mgkg

(leaf)(ii) 134mgkg

(berry)

4 weeks FISH

Lactobacilli (berryextract)

Bifidobacteria (leafand berry extracts)

Viveros et al(2011) [65]

Broilerchicks

Grape pomaceconcentrate(GPC) Grapeseed extract

(GSE)

60 gkg diet(GPC)

72 gkg diet(GSE)

(free access)

21 days Plate countT-RFLP

E coliEnterococcus sppLactobacillus spp

Lacombe et al(2013) [70] Rats Lowbush wild

blueberries

20 g feedday(eq 24 plusmn 52mganthocyaninday)

6 weeks Metagenomicsequencing

Thermonospora sppCorynebacteria spp

Slackia spp

Lactobacillus sppEnterococcus spp

summarized (Table 3) Experiments were mainly performedin rats although other larger animals such as chicks calvesor pigs have also been used Gut microbial communities wereevaluated by diverse methodologies including culture-basedmethods (plate count) DGGE FISH T-RFLP qPCR andmetagenomic sequencing

Animal studies performed in pigs [60] and in calves[61] demonstrated that tea polyphenols administration con-tributed to the improvement in the composition of the intesti-nal microbiota Thus the administration of tea polyphenolsin pigs significantly increased the levels of lactobacilli whilstit diminished the levels of total bacteria and Bacteroidaceaeand a tendency to decrease in lecithinase positive clostridiaincludingC perfringenswas also observed [60] However thereduction rate of Bifidobacterium spp and Lactobacillus sppwas slowwhile that ofC perfringensdecreased faster in calvessupplemented with the green tea extract [61]

Dolara et al [62] showed that treatment with winepolyphenols in carcinogen-treated F344 rats was associated

with a strong variation in the colonic microbiota comparedto the control-fed rats Although the total bacterial counts andanaerobeaerobe ratio of microorganisms in the feces frompolyphenol-treated rats were similar to that from control ratspropionibacteria Bacteroides and Clostridia decreased whilelactobacilli and bifidobacteria increased Based on additionalexperiments these authors concluded that reduction ofoxidative damage modulation of colonic flora and variationin gene expression may be all connected in the action of winepolyphenols on the intestinal function and carcinogenesis

In other study rats fedwith apple juice instead of drinkingwater showed more lactobacilli and bifidobacteria in freshfeces that differed from the controls by one-log10 colonyforming units [63] The same research group studied theeffect of colloids isolated from apple pomace extraction juiceson the intestinal microbiota in Wistar rats An increaseof Bacteroidaceae in almost one-log10 higher counts wasobserved in feces of rats fed with apple juice colloid thancontrol rats [64] Another animal experiment conducted to

8 BioMed Research International

study the effect on intestinal microbiota of the inclusionof grape pomace extracts in the diet of broiler chicks [65]found that for the cecum birds fed grape extracts had higherpopulations of E coli Lactobacillus and Enterococcus speciesthan birds in any other treatment group These authorsconcluded that grape polyphenol-rich products modified thegut morphology and intestinal microbiota and increased thebiodiversity degree of intestinal bacteria in broiler chicks

Inclusion of condensed tannins (proanthocyanidins)extracted from Acacia angustissima on rat diet resulted ina shift in the predominant bacteria towards tannin-resistantGram-negative Enterobacteriaceaeand Bacteroides speciesand reduced the number of Gram-positive C leptum group[66] Compatible results were obtained in an experimentwith rats fed a proanthocyanidin-rich cocoa preparation [67]where the authors found a significant decrease in the propor-tion of Bacteroides Clostridium and Staphylococcus generain the feces of cocoa-fed animals Interestingly reductions inClostridium species were found to correlate with weight lossand decrease in body mass index

Larrosa et al [68] observed an increase in lactobacilliand bifidobacteria when resveratrol (3541015840-trihydroxy-trans-stilbene) which naturally occurs in grapes and grape-derivedfoodstuffs such as red wine was administered to rats Afterinduction of colitis by dextran sulphate sodium proliferationof both E coli and enterobacteria was lower in rats treatedwith resveratrol than in control rats This could be the resultof an indirect effect of resveratrol-supplemented diet whichincreased bifidobacteria and lactobacilli counts preventingthe colonization and invasion of tissues by enterobacteriaincluding E coli

Prebiotic activity of wild blackcurrant extracts observedin in vitro experiments was further confirmed in rats byMolan et al [69] A significant increase in the populationsize of lactobacilli and bifidobacteria was observed after dailyadministration of those extracts to rats Similarly a grapeantioxidant dietary fibre preparation was found to increasethe population of Lactobacillus spp when fed to rats whereaspopulations of Bifidobacterium spp decreased and changes inE coli and Bacteroides vulgatus counts were not significant[50]

Recently Lacombe et al [70] studied the composition andfunctional potential of the colon microbiota from rats feda diet enriched in lowbush wild blueberries Application ofnovel metagenomic techniques (Illumina shotgun sequenc-ing) revealed a significant reduction in the relative abundanceof the genera Lactobacillus and Enterococcus associated withwild blueberries intake In addition hierarchical analysisshowed a significant increase in the relative abundanceof the phylum Actinobacteria the order Actinomycetalesand several novel genera under the family Bifidobacteri-aceae and Coriobacteriaceae in the blueberries group Theauthors indicated that although the microbiome of ratsdiffers from humans the applied model was a powerfultool to study population dynamics and related metabolicfunctions Metagenomic studies can determine microbialcommunity profiles gene presenceabsence and abundanceand functional repertoire however they can only infer an

observed phenotype since a gene presence does not imply itsexpression or functionality [71]

7 Human Intervention Studies

Investigations involving the use of humans potentially pro-vide the best models for studying the interactions of foodcomponents (eg polyphenols) with microbiota although invivo intervention trials hold inevitable practical and ethicallimitations [12] The use of cross-over designs where volun-teers serve as their own control permits multilevel analysisschemes that increase power but requires a relevant numberof volunteers to allow for statistically significant multivariatemodels [72] Up to now only a few studies have examinedthe in vivo impact of dietary polyphenols on the humangut microbiota and most of them were focused on singlepolyphenol molecules and selected bacterial populations Asummary of human intervention studies about effects ofpolyphenols in the modulation of the intestinal microbiotais collected in Table 4 In these studies the polyphenol doseused was much dependent on the type of food preparationand its concentration normally ranging from 01 to 4 thetreatment time was also variable from 10 days to 2 monthsand the applied microbial techniques were diverse (platecount DGGE FISH T-RFLP and qPCR)

In a study with a reduced number of subjects (119899 =8) Okubo et al [73] reported a notably increase in thepercentages of Bifidobacterium spp in total fecal countsafter an intervention with a product containing 70 of teapolyphenols A significant decrease of C perfringens andother Clostridium spp was also observed during the intakeperiod However in a crossover feeding study (number ofvolunteers not reported) that investigated the effects of blacktea drinking on hypercholesterolemic volunteers Mai et al[74] found that although specific bacterial groups were notaffected the total amount of bacteria significantly decreasedhighlighting large interindividual variations More recentlyan intervention study (119899 = 10) by Jin et al [75] confirmedan overall tendency for the proportion of bifidobacteria toincrease because of green tea consumption even thoughthere were interindividual differences in the Bifidobacteriumspecies

Yamakoshi et al [76] showed that administration of aproanthocyanidin-rich extract from grape seeds to healthyvolunteers (119899 = 9) significantly increased the fecal number ofBifidobacterium whereas the number of putrefactive bacteriasuch as enterobacteria tended to decrease The interactionbetween proanthocyanidins and intestinal bacteria was alsoconfirmed in a randomized double-blind crossover andcontrolled intervention study (119899 = 22) ingesting two cocoadrinks exhibiting low and high polyphenol content [77]Compared with the consumption of the low-flavan-3-olcocoa drink the daily consumption of the high-flavan-3-ol cocoa drink significantly increased the bifidobacteria andlactobacilli populations but significantly decreased clostridiacounts

Queipo-Ortuno et al [78] performed a randomizedcrossover and controlled trial (119899 = 10) consisting of theintake of red wine dealcoholized red wine and gin over

BioMed Research International 9

Table4Hum

aninterventio

nstu

dies

Reference

Volunteer

number

Phenolic

compo

undfood

Dose

Treatm

ent

duratio

nMicrobial

techniqu

ePo

pulatio

nincrease

Popu

latio

ndecrease

Noeffect

Oku

boetal

(1994)[73]

8Green

tea

(Sun

phenon

)04g

3tim

esper

day

4weeks

Platec

ount

Cperfr

ingens

Clostridium

spp

Yamakoshi

etal(2001)[76]

9Proantocyanidin-

richextractfrom

grapes

eeds

05g

day

6weeks

Platec

ount

Bifid

obacteriu

mspp

Enterobacteriaceae

Maietal

(200

4)[74]

15Blacktea

700m

gteas

olids5

times

perd

ay21

days

FISH

DGGE

Totalbacteria

Nochanges

Claveletal

(2005)

[83]

39Isofl

avon

es100m

gday

2mon

ths

TTGEFISH

Ccoccoides-E

rectale

grou

pBifid

obacteriu

mspp

Lactobacillus-

Enterococcus

spp

Faecalibacteriu

mprau

snitziisubgroup

Costabileetal

(2008)

[84]

31Who

legrainwheat

cereals

48gday

3weeks

FISH

Bifid

obacteria

Lactob

acilli

Totalbacteria

Bacteroidesspp

C

histo

lyticum

perfringens

grou

pAc

etobacteriu

mspp

Jaqu

etetal

(200

9)[87]

16Coff

ee3cupsday

3weeks

FISH

DGGE

Bifid

obacteriu

mspp

Carvalho

-Wellsetal

(2010)

[85]

32Who

legrainmaize

cereals

48gday

3weeks

FISH

Bifid

obacteria

Totalbacteria

Bacteroidesspp

C

histo

lyticum

perfringens

grou

pAc

etobacteriu

mspp

Gill

etal

(2010)

[80]

10Ra

spberrypu

ree

20gday

4days

PCR-DGGE

Nochangesinthep

rofileo

fcolonicb

acteria

Shinoh

arae

tal(2010)[79]

8Ap

ples

2applesday

2weeks

Platec

ount

Lactobacillus

spp

Streptococcusspp

En

terococcus

spp

Enterobacteriaceae

lecithinase-po

sitive

clostrid

iainclu

ding

Cperfr

ingens

Pseudomonas

spp

10 BioMed Research International

Table4Con

tinued

Reference

Volunteer

number

Phenolic

compo

undfood

Dose

Treatm

ent

duratio

nMicrobial

techniqu

ePo

pulatio

nincrease

Popu

latio

ndecrease

Noeffect

Tzou

nise

tal

(2011)[77]

22Cocoa

flavano

l494m

gday

29mgday

4weeks

FISH

Bifid

obacteriu

mspp

Lactobacillus

spp

Chisto

lyticum

perfringens

grou

p

Vend

ramee

tal(2011)[81]

15Wild

blueberry

drink

25gwild

blueberriesd

ay6weeks

qPCR

Bifid

obacteriu

mspp

Lacidophilus

Bacteroidesspp

Prevotellaspp

Enterococcus

spp

Ccoccoides

Queipo-

Ortun

oetal

(2012)

[78]

10Re

dwine

272m

Lday

20days

qPCR

Enterococcus

spp

Prevotellaspp

Bacteroides

Bifid

obacteriu

mspp

Bacteroidesu

niform

isEggerthella

lenta

Blautia

coccoides-E

rectaleg

roup

Clostridium

spp

Chisto

lyticum

group

Actin

obacteria

Jinetal(2012)

[75]

10Green

tea

1000

mLday

10days

T-RF

LPqP

CRBifid

obacteriu

mspp

Gug

lielm

ettiet

al(2013)[82]

15Wild

blueberries

drink

25gwild

blueberriesd

ay6weeks

qPCR

Blongum

subspinfantis

Cuervo

etal

(2014)

[86]

38

Dairy

prod

ucts

Fruits

Vegetables

Cereals

Food

intake

was

recorded

usingan

annu

alfood

frequ

ency

questio

nnaire

qPCR

Lactobacillus

Bcoccoides

Clep

tum

BioMed Research International 11

three consecutive periods After the red wine period thebacterial concentrations of proteobacteria fusobacteria Fir-micutes and Bacteroidetes markedly increased comparedwith the washout period significant increases in the num-ber of Bifidobacterium spp and Prevotella spp were alsoobserved However Lactobacillus spp Clostridium spp andC histolyticum group concentrations remained unchangedthroughout the study

In a small-scale observational study (119899 = 8) Shinoharaet al [79] found that the number of bifidobacteria in fecessignificantly increased during apple intake and the numbersof Lactobacillus spp Streptococcus spp and Enterococcusspp tended to increase On the contrary enterobacteriaand lecithinase-positive clostridia including C perfringensand Pseudomonas species tended to decrease Howeverthat study did not use culture-independent microbiologytechniques and suffered from the lack of a control groupAlso in relation to fruits another small human interventionstudy (119899 = 10) with raspberry puree [80] did not observestatistically significant alterations in the profile of colonicbacteria probably due to high interindividual variation infecal bacteria although the profiles of microbial metabolitesof raspberry polyphenols varied greatly between individualsindicating that the type of gut microbiota affects cataboliteprofiles released by bacteria in the colonThis lack of effect onthe intestinal microbiota after the intake of raspberry pureemight also be due to the short duration of the treatment aswell as the techniques employed to quantify the intestinalmicrobiota

Vendrame et al [81] studied the potential prebioticactivity of a drink elaborated fromwild blueberries especiallyrich in anthocyanins in a small intervention trial (119899 = 15) Asignificant increase in Bifidobacterium spp and L acidophilusgroup was detected while no significant differences wereobserved for Bacteroides spp Prevotella spp Enterococcusspp and C coccoides In a further paper of the same group[82] seven different intragenus bifidobacteria taxonomicclusters that were among the most common and abundantbifidobacteria species inhabiting the human gutwere targetedin the same samples It was found thatB adolescentisB breveB catenulatumpseudocatenulatum and B longum subsplongumwere always present in the group of subjects enrolledwhereas B bifidum and B longum subsp infantis were notIn spite of the large interindividual variability a significantincrease of B longum subsp infantis cell concentration wasobserved in the feces of volunteers after the wild blueberrydrink treatment which was attributed to the presence ofprebiotic (bifidogenic) molecules from blueberries possiblyfibers and glycosylated anthocyanins

In a study with postmenopausal women (119899 = 39)Clavel et al [83] found that isoflavone supplementationstimulated dominant microorganisms of the C coccoides-Erectale cluster Lactobacillus-Enterococcus group Faecalibac-terium prausnitzii subgroup and Bifidobacterium genus Itwas also suggested that the concentration of C coccoides-Erectale cluster was related to women capacity to excrete equolan intestinal metabolite from daidzein In two interventionstudies with whole grain breakfast cereals from wheat (119899 =31) and maize (119899 = 32) [84 85] the ingestion of both

products resulted in significant increases in fecal bifidobac-teria andor lactobacilli without changing the relative abun-dance of other dominant members of the gut microbiotaLittle or no changes were observed in the numbers of totalbacteria Bacteroides spp C histolyticumperfringens groupand Acetobacterium spp present in the feces However aswhole grains are good sources of dietary fiber it is difficult toascribe the observed effects only to the phenolic compoundspresent in these foods In this respect Cuervo et al [86] haverecently studied the correlations between the intake of fiberand polyphenols from diet and fecal microbiota compositionin a cohort of apparently healthy subjects Results showedthat the intake of soluble pectins and flavanones fromorangespresented a negative correlation with the levels of B coccoidesand C leptum By contrast the intake of white breadproviding hemicellulose and resistant starch was directlycorrelated with Lactobacillus

Finally another human trial (119899 = 16) carried out byJaquet et al [87] assessed the impact of a moderate con-sumption of instant coffee on the general composition ofthe human intestinal bacterial population Coffee bever-ages contain significant amounts of soluble fibre (mainlygalactomannans and arabinogalactan-proteins) and phenoliccompounds (chlorogenic acids) which arewell utilised by thehuman fecal microbiota It was observed that although fecalprofiles of the dominant microbiota were not significantlyaffected after the consumption of the coffee the populationof Bifidobacterium spp increased being the largest increaseobserved for those volunteers showing the lowest initialbifidobacteria levels

8 Conclusions

This review has tried to summarize the current knowledgein relation to the phenolic metabolism by gut microbiota andthemodulation of the gutmicrobiota by phenolic compoundsand polyphenol-rich dietary sourcesThere are evidences thatthe beneficial effects attribute to dietary polyphenols dependon their biotransformation by the gut microbiota Thereforeit is important to investigate the bacterial species impli-cated in the metabolism of dietary polyphenols and furtherresearch is still needed in relation to the resultant microbialmetabolites to ascertain their mechanisms of action Onthe other hand a great number of in vitro and in vivo (inanimals andhumans) studies showing the influence of dietarypolyphenols on gut-inhabiting bacteria have been publishedin recent years Although in vitro assays facilitate experimen-tation caution must be taken in extrapolating results to invivo situation as many factors are acting upon this processIn general in both in vitro and in vivo studies polyphenols orpolyphenol-rich sources have shown to influence the relativeabundance of different bacterial groups within the gut micro-biota reducing numbers of potential pathogens including Cperfringens and C histolyticum and certain Gram-negativeBacteroides spp and enhancing mainly beneficial Clostridiabifidobacteria and lactobacilli A better understanding of theinteraction between dietary polyphenols and gut microbiotathrough the emerging advances in high-throughput meta-genomic transcriptomic and proteomic approaches would

12 BioMed Research International

be essential in order to identify genes and micro-organismsinvolved in polyphenol (in)activation and conversion andthus to elucidate the implications of diet on the modulationof microbiota for delivering health benefits

Functional foods are considered to enhance the protectiveeffects against diseases derived from some food componentsIn the last decades dairy fermented foods have probablybeen one of the most-developed functional products andhave deserved intensive research In this expansion dairyfermented foods have been supplemented with fruits cerealsand other stuffs of plant origin all of which represent a highpercentage of the current market of the dairy industry Theseproducts have a healthy appeal which attracts consumersThus fruit juicesconcentrates and prepared fruits (in theform of pieces pulp and even flour) have been successfullyincorporated in dairy fermented foods as sources of prebioticfibers and phytochemicals Among these phytochemicalspresent in plant-derived foods polyphenols have gainedmuch interest due to their diverse potential beneficial effectsin human health The supplementation of dairy fermentedproducts with rich-polyphenolic stuffs (phenolic extractsphenolic-enriched fractions etc) seems to be an effectivetechnological option to improve the benefits of these productsin the balance of the intestinal microbiota due not only to theaction of the probiotics but also to the potential modulationeffects exerted by polyphenols as it has been described in thisreview Further research in this area will aim to accomplishthe benefits of both probiotic strains and polyphenols inrelation to gut health

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors of this review were funded by the SpanishMINECO through different projects (AGL2012-40172-C02-01 AGL2010-17499 and BFU2012-35228) and the CON-SOLIDER INGENIO 2010 programme (project FUN-C-FOOD CSD2007-063) as well as Comunidad de Madrid(project ALIBIRD P2009AGR-1469) Montserrat Duenaswould like to thank the Spanish ldquoRamon y Cajalrdquo Programmefor a contract

References

[1] S E Power P W OrsquoToole C Stanton R P Ross and GF Fitzgerald ldquoIntestinal microbiota diet and healthrdquo BritishJournal of Nutrition vol 111 no 3 pp 387ndash402 2014

[2] PDeCruz L Prideaux JWagner et al ldquoCharacterization of thegastrointestinal microbiota in health and inflammatory boweldiseaserdquo Inflammatory Bowel Diseases vol 18 no 2 pp 372ndash390 2012

[3] A Kramer S Bekeschus B M Broker H Schleibinger BRazavi and O Assadian ldquoMaintaining health by balancingmicrobial exposure and prevention of infection the hygienehypothesis versus the hypothesis of early immune challengerdquoJournal of Hospital Infection vol 83 no 1 pp S29ndashS34 2013

[4] M Rescigno ldquoIntestinal microbiota and its effects on theimmune systemrdquo Cellular Microbiology vol 16 no 7 pp 1004ndash1013 2014

[5] M G L Hertog E J M Feskens P C H HollmanM B Katanand D Kromhout ldquoDietary antioxidant flavonoids and risk ofcoronary heart disease the Zutphen Elderly StudyrdquoThe Lancetvol 342 no 8878 pp 1007ndash1011 1993

[6] I C W Arts and P C H Hollman ldquoPolyphenols and diseaserisk in epidemiologic studiesrdquoThe American Journal of ClinicalNutrition vol 81 no 1 pp 317Sndash325S 2009

[7] D del Rio A Rodriguez-Mateos J P E Spencer M TognoliniG Borges and A Crozier ldquoDietary (poly)phenolics in humanhealth structures bioavailability and evidence of protectiveeffects against chronic diseasesrdquo Antioxidants amp Redox Signal-ing vol 18 no 14 pp 1818ndash1892 2013

[8] F Perez-Vizcaino and J Duarte ldquoFlavonols and cardiovasculardiseaserdquo Molecular Aspects of Medicine vol 31 no 6 pp 478ndash494 2010

[9] J P E Spencer K Vafeiadou R J Williams and D VauzourldquoNeuroinflammation modulation by flavonoids and mecha-nisms of actionrdquo Molecular Aspects of Medicine vol 33 no 1pp 83ndash97 2012

[10] J M Laparra and Y Sanz ldquoInteractions of gut microbiota withfunctional food components and nutraceuticalsrdquo Pharmacolog-ical Research vol 61 no 3 pp 219ndash225 2010

[11] X He M L Marco and C M Slupsky ldquoEmerging aspects offood and nutrition on gut microbiotardquo Journal of Agriculturaland Food Chemistry vol 61 no 40 pp 9559ndash9574 2013

[12] D Hervert-Hernandez and I Goni ldquoDietary polyphenols andhuman gut microbiota a reviewrdquo Food Reviews Internationalvol 27 no 2 pp 154ndash169 2011

[13] K M Tuohy L Conterno M Gasperotti and R Viola ldquoUp-regulating the human intestinal microbiome using whole plantfoods polyphenols andor fiberrdquo Journal of Agricultural andFood Chemistry vol 60 no 36 pp 8776ndash8782 2012

[14] U Etxeberria A Fernandez-Quintela F I Milagro L AguirreJ A Martınez and M P Portillo ldquoImpact of polyphenols andpolyphenol-rich dietary sources on gut microbiota composi-tionrdquo Journal of Agricultural and Food Chemistry vol 61 no 40pp 9517ndash9533 2013

[15] F Cardona C Andres-Lacueva S Tulipani F J Tinahonesand M I Queipo-Ortuno ldquoBenefits of polyphenols on gutmicrobiota and implications in human healthrdquo Journal ofNutritional Biochemistry vol 24 no 8 pp 1415ndash1422 2013

[16] M V Selma J C Espın and F A Tomas-Barberan ldquoInteractionbetween phenolics and gut microbiota role in human healthrdquoJournal of Agricultural and Food Chemistry vol 57 no 15 pp6485ndash6501 2009

[17] T RequenaMMonagasM A Pozo-Bayon et al ldquoPerspectivesof the potential implications ofwine polyphenols on humanoraland gut microbiotardquo Trends in Food Science amp Technology vol21 no 7 pp 332ndash344 2010

[18] J Van Duynhoven E E Vaughan F van Dorsten et alldquoInteractions of black tea polyphenols with human gut micro-biota implications for gut and cardiovascular health1-4rdquo TheAmerican Journal of Clinical Nutrition vol 98 no 6 pp 1631Sndash1641S 2013

[19] SMoco F-P JMartin and S Rezzi ldquoMetabolomics view on gutmicrobiome modulation by polyphenol-rich foodsrdquo Journal ofProteome Research vol 11 no 10 pp 4781ndash4790 2012

BioMed Research International 13

[20] R K Buddington and P T Sangild ldquoCompanion animalssymposium development of the mammalian gastrointestinaltract the resident microbiota and the role of diet in early liferdquoJournal of Animal Science vol 89 no 5 pp 1506ndash1519 2011

[21] K Tiihonen A C Ouwehand and N Rautonen ldquoHumanintestinal microbiota and healthy ageingrdquo Ageing ResearchReviews vol 9 no 2 pp 107ndash116 2010

[22] D Mariat O Firmesse F Levenez et al ldquoThe firmicutesbacteroidetes ratio of the human microbiota changes with agerdquoBMCMicrobiology vol 9 article 123 2009

[23] M Arumugam J Raes E Pelletier et al ldquoEnterotypes of thehuman gutmicrobiomerdquoNature vol 473 no 7346 pp 174ndash1802011

[24] G D Wu J Chen C Hoffmann et al ldquoLinking long-termdietary patterns with gut microbial enterotypesrdquo Science vol334 no 6052 pp 105ndash108 2011

[25] I B JefferyM J Claesson PWOrsquoToole and F Shanahan ldquoCat-egorization of the gut microbiota enterotypes or gradientsrdquoNature Reviews Microbiology vol 10 no 9 pp 591ndash592 2012

[26] WM de Vos andM Nieuwdorp ldquoGenomics a gut predictionrdquoNature vol 498 no 7452 pp 48ndash49 2013

[27] P B Eckburg E M Bik C N Bernstein et al ldquoMicrobiologydiversity of the human intestinal microbial florardquo Science vol308 no 5728 pp 1635ndash1638 2005

[28] E G Zoetendal C T Collier S Koike R I Mackie and H RGaskins ldquoMolecular ecological analysis of the gastrointestinalmicrobiota a reviewrdquo Journal of Nutrition vol 134 no 2 pp465ndash472 2004

[29] M H Fraher PW OrsquoToole and E MM Quigley ldquoTechniquesused to characterize the gut microbiota a guide for the clini-cianrdquo Nature Reviews Gastroenterology and Hepatology vol 9no 6 pp 312ndash322 2012

[30] R A Kemperman S Bolca L C Roger and E E VaughanldquoNovel approaches for analysing gut microbes and dietarypolyphenols challenges and opportunitiesrdquo Microbiology vol156 no 11 pp 3224ndash3231 2010

[31] R A Kemperman G Gross S Mondot et al ldquoImpact ofpolyphenols from black tea and red winegrape juice on a gutmodel microbiomerdquo Food Research International vol 53 no 2pp 659ndash669 2013

[32] M N Clifford ldquoDiet-derived phenols in plasma and tissues andtheir implications for healthrdquo Planta Medica vol 70 no 12 pp1103ndash1114 2004

[33] A Crozier D del Rio and M N Clifford ldquoBioavailability ofdietary flavonoids and phenolic compoundsrdquoMolecular Aspectsof Medicine vol 31 no 6 pp 446ndash467 2010

[34] A J Day M S Dupont S Ridley et al ldquoDeglycosylation offlavonoid and isoflavonoid glycosides by human small intestineand liver beta-glucosidase activityrdquo FEBS Letters vol 436 no 1pp 71ndash75 1998

[35] A J Day F J Canada J C Dıaz et al ldquoDietary flavonoid andisoflavone glycosides are hydrolysed by the lactase site of lactasephlorizin hydrolaserdquo FEBS Letters vol 468 no 2-3 pp 166ndash1702000

[36] A Scalbert and G Williamson ldquoDietary intake and bioavail-ability of polyphenolsrdquo Journal of Nutrition vol 130 no 8 pp2073Sndash2085S 2000

[37] A R Rechner G Kuhnle H Hu et al ldquoThe metabolism ofdietary polyphenols and the relevance to circulating levels ofconjugated metabolitesrdquo Free Radical Research vol 36 no 11pp 1229ndash1241 2002

[38] A-M Aura K A OrsquoLeary G Williamson et al ldquoQuercetinderivatives are deconjugated and converted to hydroxypheny-lacetic acids but not methylated by human fecal flora in vitrordquoJournal of Agricultural and Food Chemistry vol 50 no 6 pp1725ndash1730 2002

[39] A-M Aura ldquoMicrobial metabolism of dietary phenolic com-pounds in the colonrdquo Phytochemistry Reviews vol 7 no 3 pp407ndash429 2008

[40] M Monagas M Urpi-Sarda F Sanchez-Patan et al ldquoInsightsinto themetabolism andmicrobial biotransformation of dietaryflavan-3-ols and the bioactivity of their metabolitesrdquo Food andFunction vol 1 no 3 pp 233ndash253 2010

[41] GWilliamson andMNClifford ldquoColonicmetabolites of berrypolyphenols the missing link to biological activityrdquo BritishJournal of Nutrition vol 104 no 3 pp S48ndashS66 2010

[42] D M Jacobs E Gaudier J van Duynhoven and E E VaughanldquoNon-digestible food ingredients colonic microbiota and theimpact on gut health and immunity a role for metabolomicsrdquoCurrent Drug Metabolism vol 10 no 1 pp 41ndash54 2009

[43] S Bolca S Possemiers V Maervoet et al ldquoMicrobial anddietary factors associatedwith the 8-prenylnaringenin producerphenotype a dietary intervention trial with fifty healthy post-menopausal Caucasian womenrdquo British Journal of Nutritionvol 98 no 5 pp 950ndash959 2007

[44] X Tzounis J Vulevic G G C Kuhnle et al ldquoFlavanolmonomer-induced changes to the human faecal microflorardquoBritish Journal of Nutrition vol 99 no 4 pp 782ndash792 2008

[45] M Hidalgo M J Oruna-Concha S Kolida et al ldquoMetabolismof anthocyanins by human gut microflora and their influenceon gut bacterial growthrdquo Journal of Agricultural and FoodChemistry vol 60 no 15 pp 3882ndash3890 2012

[46] A L Molan M A Lila J Mawson and S De ldquoIn vitroand in vivo evaluation of the prebiotic activity of water-soluble blueberry extractsrdquo World Journal of Microbiology andBiotechnology vol 25 no 7 pp 1243ndash1249 2009

[47] D Bialonska P Ramnani S G Kasimsetty K R Muntha GR Gibson and D Ferreira ldquoThe influence of pomegranate by-product and punicalagins on selected groups of human intesti-nal microbiotardquo International Journal of FoodMicrobiology vol140 no 2-3 pp 175ndash182 2010

[48] G Mandalari R M Faulks C Bisignano K W Waldron ANarbad and M S J Wickham ldquoIn vitro evaluation of theprebiotic properties of almond skins (Amygdalus communisL)rdquoFEMS Microbiology Letters vol 304 no 2 pp 116ndash122 2010

[49] V Fogliano M L Corollaro P Vitaglione et al ldquoIn vitro bioac-cessibility and gut biotransformation of polyphenols present inthe water-insoluble cocoa fractionrdquoMolecular Nutritionamp FoodResearch vol 55 supplement 1 pp S44ndashS55 2011

[50] M J Pozuelo A Agis-Torres D Hervert-Hernandez etal ldquoGrape antioxidant dietary fiber stimulates Lactobacillusgrowth in rat cecumrdquo Journal of Food Science vol 77 no 2 ppH59ndashH62 2012

[51] C Cueva F Sanchez-Patan M Monagas et al ldquoIn vitrofermentation of grape seed flavan-3-ol fractions by humanfaecal microbiota changes in microbial groups and phenolicmetabolitesrdquo FEMSMicrobiology Ecology vol 83 no 3 pp 792ndash805 2013

[52] F Sanchez-Patan C CuevaMMonagas et al ldquoIn vitro fermen-tation of a red wine extract by human gut microbiota changesin microbial groups and formation of phenolic metabolitesrdquoJournal of Agricultural and Food Chemistry vol 60 no 9 pp2136ndash2147 2012

14 BioMed Research International

[53] E Barroso F Sanchez-Patan P J Martın-Alvarez et al ldquoLacto-bacillus plantarum IFPL935 favors the initial metabolism of redwine polyphenols when added to a colonic microbiotardquo Journalof Agricultural and Food Chemistry vol 61 no 42 pp 10163ndash10172 2013

[54] G R Gibson J H Cummings and G T Macfarlane ldquoUse ofa three-stage continuous culture system to study the effect ofmucin on dissimilatory sulfate reduction and methanogenesisby mixed populations of human gut bacteriardquo Applied andEnvironmentalMicrobiology vol 54 no 11 pp 2750ndash2755 1988

[55] KMollyMVandeWoestyne andWVerstraete ldquoDevelopmentof a 5-step multi-chamber reactor as a simulation of thehuman intestinal microbial ecosystemrdquo Applied Microbiologyand Biotechnology vol 39 no 2 pp 254ndash258 1993

[56] M Minekus M Smeets-Peeters A Bernalier et al ldquoAcomputer-controlled system to simulate conditions of thelarge intestine with peristaltic mixing water absorption andabsorption of fermentation productsrdquoAppliedMicrobiology andBiotechnology vol 53 no 1 pp 108ndash114 1999

[57] PDeBoever BDeplancke andWVerstraete ldquoFermentation bygut microbiota cultured in a simulator of the human intestinalmicrobial ecosystem is improved by supplementing a soygermpowderrdquo Journal of Nutrition vol 130 no 10 pp 2599ndash26062000

[58] C S Yang X Wang G Lu and S C Picinich ldquoCancerprevention by tea animal studies molecular mechanisms andhuman relevancerdquoNature Reviews Cancer vol 9 no 6 pp 429ndash439 2009

[59] R E Ley F Backhed P Turnbaugh C A Lozupone R DKnight and J I Gordon ldquoObesity alters gut microbial ecologyrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 102 no 31 pp 11070ndash11075 2005

[60] H Hara N Orita S Hatano et al ldquoEffect of tea polyphenols onfecal flora and fecal metabolic products of pigsrdquo The Journal ofVeterinary Medical Science vol 57 no 1 pp 45ndash49 1995

[61] N Ishihara D-C Chu S Akachi and L R Juneja ldquoImprove-ment of intestinal microflora balance and prevention of diges-tive and respiratory organ diseases in calves by green teaextractsrdquo Livestock Production Science vol 68 no 2-3 pp 217ndash229 2001

[62] P Dolara C Luceri C De Filippo et al ldquoRed wine polyphenolsinfluence carcinogenesis intestinal microflora oxidative dam-age and gene expression profiles of colonicmucosa in F344 ratsrdquoMutation Research-Fundamental and Molecular Mechanisms ofMutagenesis vol 591 no 1-2 pp 237ndash246 2005

[63] S Sembries G Dongowski K Mehrlander F Will and HDietrich ldquoPhysiological effects of extraction juices from applegrape and red beet pomaces in ratsrdquo Journal of Agricultural andFood Chemistry vol 54 no 26 pp 10269ndash10280 2006

[64] S Sembries G Dongowski G Jacobasch K Mehrlander FWill andH Dietrich ldquoEffects of dietary fibre-rich juice colloidsfrom apple pomace extraction juices on intestinal fermentationproducts and microbiota in ratsrdquo British Journal of Nutritionvol 90 no 3 pp 607ndash615 2003

[65] A Viveros S Chamorro M Pizarro I Arija C Centeno andA Brenes ldquoEffects of dietary polyphenol-rich grape productson intestinal microflora and gut morphology in broiler chicksrdquoPoultry Science vol 90 no 3 pp 566ndash578 2011

[66] A H Smith and R I Mackie ldquoEffect of condensed tannins onbacterial diversity andmetabolic activity in the rat gastrointesti-nal tractrdquo Applied and Environmental Microbiology vol 70 no2 pp 1104ndash1115 2004

[67] M Massot-Cladera T Perez-Berezo A Franch M Castelland F J Perez-Cano ldquoCocoa modulatory effect on rat faecalmicrobiota and colonic crosstalkrdquo Archives of Biochemistry andBiophysics vol 527 no 2 pp 105ndash112 2012

[68] M Larrosa M J Yanez-Gascon M V Selma et al ldquoEffectof a low dose of dietary resveratrol on colon microbiotainflammation and tissue damage in a DSS-induced colitis ratmodelrdquo Journal of Agricultural and Food Chemistry vol 57 no6 pp 2211ndash2220 2009

[69] A-L Molan Z Liu andM Kruger ldquoThe ability of blackcurrantextracts to positively modulate key markers of gastrointestinalfunction in ratsrdquoWorld Journal ofMicrobiologyampBiotechnologyvol 26 no 10 pp 1735ndash1743 2010

[70] A Lacombe R W Li D Klimis-Zacas et al ldquoLowbush wildblueberries have the potential to modify gut microbiota andxenobiotic metabolism in the rat colonrdquo PLoS ONE vol 8 no6 Article ID e67497 2013

[71] R Saad M R Rizkallah and R K Aziz ldquoGut Pharmacomicro-biomics the tip of an iceberg of complex interactions betweendrugs and gut-associated microbesrdquo Gut Pathogens vol 4 no1 article 16 2012

[72] E J J Van Velzen J A Westerhuis J P M van Duynhovenet al ldquoMultilevel data analysis of a crossover designed humannutritional intervention studyrdquo Journal of Proteome Researchvol 7 no 10 pp 4483ndash4491 2008

[73] T Okubo N Ishihara H Takahashi et al ldquoEffects of partiallyhydrolyzed guar gum intake on human intestinal microfloraand itsmetabolismrdquoBioscience Biotechnology andBiochemistryvol 58 no 8 pp 1364ndash1369 1994

[74] V Mai H A Katki H Harmsen et al ldquoEffects of a controlleddiet and black tea drinking on the fecalmicroflora compositionand the fecal bile acid profile of human volunteers in a double-blinded ramdomized feeding studyrdquo The Journal of Nutritionvol 134 no 2 pp 473ndash478 2004

[75] J-S Jin M Touyama T Hisada and Y Benno ldquoEffectsof green tea consumption on human fecal microbiota withspecial reference to Bifidobacterium speciesrdquoMicrobiology andImmunology vol 56 no 11 pp 729ndash739 2012

[76] J Yamakoshi S Tokutake M Kikuchi Y Kubota H Konishiand T Mitsuoka ldquoEffect of proantocyanidin -rich extract fromgrape seed on human fecal flora and fecalodorrdquo FASEB Journalvol 15 no 4 p A633 2001

[77] X Tzounis A Rodriguez-Mateos J Vulevic G R Gibson CKwik-Uribe and J P E Spencer ldquoPrebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomizedcontrolled double-blind crossover intervention studyrdquo TheAmerican Journal of Clinical Nutrition vol 93 no 1 pp 62ndash722011

[78] M I Queipo-Ortuno M Boto-Ordonez M Murri et alldquoInfluence of red wine polyphenols and ethanol on the gutmicrobiota ecology and biochemical biomarkersrdquo AmericanJournal of Clinical Nutrition vol 95 no 6 pp 1323ndash1334 2012

[79] K Shinohara Y Ohashi K Kawasumi A Terada and TFujisawa ldquoEffect of apple intake on fecal microbiota andmetabolites in humansrdquo Anaerobe vol 16 no 5 pp 510ndash5152010

[80] C I R Gill G J Mcdougall S Glidewell et al ldquoProfiling ofphenols in human fecal water after raspberry supplementationrdquoJournal of Agricultural and Food Chemistry vol 58 no 19 pp10389ndash10395 2010

[81] S Vendrame S Guglielmetti P Riso S Arioli D Klimis-Zacasand M Porrini ldquoSix-week consumption of a wild blueberry

BioMed Research International 15

powder drink increases Bifidobacteria in the human gutrdquoJournal of Agricultural and Food Chemistry vol 59 no 24 pp12815ndash12820 2011

[82] S Guglielmetti D Fracassetti V Taverniti et al ldquoDifferentialmodulation of human intestinal Bifidobacterium populationsafter consumption of a wild blueberry (Vaccinium angusti-folium) drinkrdquo Journal of Agricultural and Food Chemistry vol61 no 34 pp 8134ndash8140 2013

[83] T Clavel M Fallani P Lepage et al ldquoIsoflavones and func-tional foods alter the dominant intestinal microbiota in post-menopausal womenrdquo Journal of Nutrition vol 135 no 12 pp2786ndash2792 2005

[84] A Costabile A Klinder F Fava et al ldquoWhole-grain wheatbreakfast cereal has a prebiotic effect on the human gut micro-biota a double-blind placebo-controlled crossover studyrdquoBritish Journal of Nutrition vol 99 no 1 pp 110ndash120 2008

[85] A L Carvalho-Wells K Helmolz C Nodet et al ldquoDetermina-tion of the in vivo prebiotic potential of a maize-based wholegrain breakfast cereal a human feeding studyrdquo British Journalof Nutrition vol 104 no 9 pp 1353ndash1356 2010

[86] A Cuervo L Valdes N Salazar et al ldquoPilot study of diet andmicrobiota interactive associations of fibers and polyphenolswith human intestinal bacteriardquo Journal of Agricultural andFood Chemistry vol 62 no 23 pp 5330ndash5336 2014

[87] M Jaquet I Rochat J Moulin C Cavin and R BibilonildquoImpact of coffee consumption on the gut microbiota a humanvolunteer studyrdquo International Journal of FoodMicrobiology vol130 no 2 pp 117ndash121 2009

Submit your manuscripts athttpwwwhindawicom

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International Journal of

Microbiology

Page 5: Review Article A Survey of Modulation of Gut Microbiota by ...downloads.hindawi.com/journals/bmri/2015/850902.pdf · Review Article A Survey of Modulation of Gut Microbiota by Dietary

BioMed Research International 5

Table1Stud

iesu

singbatchcultu

referm

entatio

n

Reference

Fecal

concentration

Phenolic

compo

undfood

Dose

Timeo

fincubatio

nMicrobial

techniqu

eGrowth

enhancem

ent

Growth

inhibitio

nNoeffect

Tzou

nise

tal

(2008)

[44]

10w

v(+)-catechin

150m

gL

1000

mgL

lt48

hFISH

Lactobacillus-

Enterococcus

spp

Bifid

obacteriu

mspp

Ccoccoides-E

rectale

grou

pE

coli

Chisto

lyticum

grou

p

Molan

etal(2009)

[46]

01

vv

Blueberryextracts

510

and25

48h

FISH

Lactob

acilli

Bifid

obacteria

Bialon

skae

tal

(2010)

[47]

10w

vPo

megranate

extractand

punicalagin

10

48h

FISH

Totalbacteria

Bifid

obacteriu

mspp

Lactobacillus-

Enterococcus

spp

Ccoccoides-E

rectale

grou

pC

histo

lyticum

grou

p

Mandalarietal

(2010)

[48]

10w

vAlm

ondskins

1w

vpredigested

almon

dskins

lt24

hFISH

Bifid

obacteria

Ccoccoides-E

rectale

grou

p

Chisto

lyticum

grou

p

Fogliano

etal

(2011)[49]

5w

vWater-in

soluble

cocoafraction

1w

v36

hFISH

Bifid

obacteria

Lactob

acilli

Cuevae

tal(2013)

[51]

10w

vGrape

seed

extract

fractio

ns300ndash

450m

gL

lt48

hFISH

Lactobacillus-

Enterococcus

spp

Chisto

lyticum

grou

p

Hidalgo

etal

(2012)

[45]

10w

v

Malvidin-3-O-

glucoside

Antho

cyanidins

mixture

20mgLand

200m

gL

4850

mgLand

48500m

gL

lt24

hFISH

Lactobacillus-

Enterococcus

spp

Bifid

obacteriu

mspp

Ccoccoides-E

rectale

grou

p

Sanchez-Patanet

al(2012)[52]

1wv

Redwinee

xtract

600m

gL

48h

FISH

Chisto

lyticum

grou

p

Lactobacillus-

Enterococcus

spp

Barrosoetal

(2013)

[53]

Redwinee

xtract

500m

gL

48h

qPCR

Lactobacillus

spp

Bifid

obacteriu

mspp

Bacteroidesspp

Ru

minococcusspp

6 BioMed Research International

Table 2 Studies using the gastrointestinal simulators (ie SHIME)

Reference Simulator Phenoliccompoundfood Dose Time Microbial

techniquePopulationincrease Population decrease

De Boeveret al (2000)[57]

SHIME Soy germ powder 25 gday 2 weeks Plate count

EnterobacteriaceaeColiforms

Lactobacillus sppStaphylococcus sppClostridium spp

Kempermanet al (2013)[31]

Twin-SHIME Black tea extract

3 times dailydosing(1000mg

polyphenolsas total daily

dose)

2 weeks

Plate countqPCR

PCR-DGGEpyrosequencing

Klebsiella sppEnterococci

Akkermansia spp

BifidobacteriaBlautia coccoidesAnaeroglobus sppVictivallis spp

Kempermanet al (2013)[31]

Twin-SHIME

Red wine-grapeextract

3 times dailydosing(1000mg

polyphenolsas total daily

dose)

2 weeks

Plate countqPCR

PCR-DGGEpyrosequencing

Klebsiella sppAlistipes spp

Cloacibacillus sppVictivallis spp

Akkermansia spp

BifidobacteriaBlautia coccoides

groupAnaeroglobus spp

Subdoligranulum sppBacteroides

5 Studies Using HumanGastrointestinal Simulators

In contrast to short-duration experiments with static gutmodels longer-term experiments are required when theadaptation of the gut microbial community to dietarypolyphenols needs to be assessed To this end dynamic invitro gut models such as the ldquoReadingrdquo model [54] theSimulator of the Human Intestinal Microbial Ecosystem(SHIME) the TNO Intestinal Model 2 (TIM2) [55 56] andthe recent gastrointestinal simulator set up in our Institute(SIMGI) (unpublished work) have been developed where gutmicrobiota are cultured over a longer time frame (days toweeks) in one or multiple connected pH controlled vesselsrepresenting different parts of the gastrointestinal tract

As an example of the versatility and potential of humangastrointestinal simulators Table 2 reports a series of studiesabout modulation of gut microbiota by polyphenols usingthe SHIME [57 58]This validatedmodel comprises stomachand small intestinal sections for predigestion of food aswell as vessels stimulating the ascending transcending anddescending parts of the human colon allowing assessment ofchanges in the different colonic areas that are very challengingto access in a human intervention However it should beunderlined that this approach takes for granted that theextracts reach intact the colonic region and no nutrientabsorption is consideredThe use of the SHIME to investigatethe effects of a soy germ powder on the fermentative capacityof the simulated microbiota of the colon was the aim of astudy carried out by De Boever et al [57]They observed thatthe addition of the soy germ powder in a 2-week treatmentresulted into an overall increase of bacterial marker pop-ulations (Enterobacteriaceae coliforms Lactobacillus sppStaphylococcus spp and Clostridium spp) with a significantincrease of 2 log10 units in the Lactobacillus spp populationMore recently Kemperman et al [31] using the twin-SHIME

model studied the influence of a bolus dose and a 2-weekcontinuous administration of complex dietary polyphenolsfrom black tea or red wine grape extracts on the colonicmicrobiota The Twin-SHIME system involving two modelsthat run in parallel was inoculatedwith the same fecal samplefor direct comparison of the effect of the two polyphenoltypes A combination of analyses including cultivation PCR-denaturing gradient gel electrophoresis (DGGE) quantita-tive PCR and high throughput pyrosequencing of the 16Sribosomal RNA gene was applied to characterize micro-bial community changes This study showed that complexpolyphenols in the context of a model system can modulateselect members of the human gut microbiota revealing noveltargets potentially involved in polyphenolmetabolism andorresistant microbes to be further investigated for polyphenolmetabolism or resistance mechanisms [31]

6 Animal Models Studies

It is widely assumed that preliminary evidence should bewarranted in animal models before human interventiontrials Animal models contribute to better understanding themechanisms and biological effects that could be likely tohappen in the human body The metabolism of polyphenolshas been object of numerous animal studies (mostly inrodents) especially for their impact on metabolic disorders[58] but only a few of these studies have followed thedynamics and composition of the intestinal microbiota inassociation with polyphenol metabolites retrieved from thehost Caution is required in extrapolating results to humansbecause culture-independent comparisons have revealed thatmost bacterial genera and species found in mice are not seenin humans although the distal gut microbiota of mice andhumans harbors the same bacterial phyla [59] In this sectionstudies performed in animals in order to assess the effects ofpolyphenols on the modulation of intestinal microbiota are

BioMed Research International 7

Table 3 Animal model studies

Reference Animal Phenoliccompoundfood Dose Treatment

durationMicrobialtechnique Population increase Population decrease

Hara et al(1995) [60] Pigs Tea polyphenols 02 (free access) 2 weeks Plate count Lactobacilli

Total bacteriaBacteroidaceaeC perfringens

Ishihara et al(2001) [61] Calves Green tea extracts 15 gday 4 weeks Plate count

Bifidobacterium sppLactobacillus sppC perfringens

Smith andMackie (2004)[66]

Rats

Proantocyanidinsextracted from

Acaciaangustissima

07 (low tannindiet) and 20

(high tannin diet)

35 weekstreatment +35 weekswashout

PCR-DGGEDot blot

hybridization

Bacteroides fragilisgroup

Bacteroides-Prevotella-

Porphyromonas group

Enterobacteriaceae

C leptum group

Dolara et al(2005) [62] Rats

Red winepolyphenolspowder

50mgkg 16 weeks Plate count LactobacilliBifidobacteria

PropionibacteriaBacteroidesClostridia

Sembries et al(2006) [63] Rats Apple juice free access 4 weeks Plate count Lactobacilli

BifidobacteriaSembries et al(2003) [64] Rats Apple pomace

juice colloid5 suppl diet(free access) 6 weeks Plate count

FISH Bacteroidaceae

Larrosa et al(2009) [68] Rats Resveratrol 1mgkgday 25 days Plate count Lactobacilli

Bifidobacteria

Molan et al(2010) [69] Rats

Blackcurrantextracts (leaf or

berry)

3 timesweek(i) 30mgkg

(leaf)(ii) 134mgkg

(berry)

4 weeks FISH

Lactobacilli (berryextract)

Bifidobacteria (leafand berry extracts)

Viveros et al(2011) [65]

Broilerchicks

Grape pomaceconcentrate(GPC) Grapeseed extract

(GSE)

60 gkg diet(GPC)

72 gkg diet(GSE)

(free access)

21 days Plate countT-RFLP

E coliEnterococcus sppLactobacillus spp

Lacombe et al(2013) [70] Rats Lowbush wild

blueberries

20 g feedday(eq 24 plusmn 52mganthocyaninday)

6 weeks Metagenomicsequencing

Thermonospora sppCorynebacteria spp

Slackia spp

Lactobacillus sppEnterococcus spp

summarized (Table 3) Experiments were mainly performedin rats although other larger animals such as chicks calvesor pigs have also been used Gut microbial communities wereevaluated by diverse methodologies including culture-basedmethods (plate count) DGGE FISH T-RFLP qPCR andmetagenomic sequencing

Animal studies performed in pigs [60] and in calves[61] demonstrated that tea polyphenols administration con-tributed to the improvement in the composition of the intesti-nal microbiota Thus the administration of tea polyphenolsin pigs significantly increased the levels of lactobacilli whilstit diminished the levels of total bacteria and Bacteroidaceaeand a tendency to decrease in lecithinase positive clostridiaincludingC perfringenswas also observed [60] However thereduction rate of Bifidobacterium spp and Lactobacillus sppwas slowwhile that ofC perfringensdecreased faster in calvessupplemented with the green tea extract [61]

Dolara et al [62] showed that treatment with winepolyphenols in carcinogen-treated F344 rats was associated

with a strong variation in the colonic microbiota comparedto the control-fed rats Although the total bacterial counts andanaerobeaerobe ratio of microorganisms in the feces frompolyphenol-treated rats were similar to that from control ratspropionibacteria Bacteroides and Clostridia decreased whilelactobacilli and bifidobacteria increased Based on additionalexperiments these authors concluded that reduction ofoxidative damage modulation of colonic flora and variationin gene expression may be all connected in the action of winepolyphenols on the intestinal function and carcinogenesis

In other study rats fedwith apple juice instead of drinkingwater showed more lactobacilli and bifidobacteria in freshfeces that differed from the controls by one-log10 colonyforming units [63] The same research group studied theeffect of colloids isolated from apple pomace extraction juiceson the intestinal microbiota in Wistar rats An increaseof Bacteroidaceae in almost one-log10 higher counts wasobserved in feces of rats fed with apple juice colloid thancontrol rats [64] Another animal experiment conducted to

8 BioMed Research International

study the effect on intestinal microbiota of the inclusionof grape pomace extracts in the diet of broiler chicks [65]found that for the cecum birds fed grape extracts had higherpopulations of E coli Lactobacillus and Enterococcus speciesthan birds in any other treatment group These authorsconcluded that grape polyphenol-rich products modified thegut morphology and intestinal microbiota and increased thebiodiversity degree of intestinal bacteria in broiler chicks

Inclusion of condensed tannins (proanthocyanidins)extracted from Acacia angustissima on rat diet resulted ina shift in the predominant bacteria towards tannin-resistantGram-negative Enterobacteriaceaeand Bacteroides speciesand reduced the number of Gram-positive C leptum group[66] Compatible results were obtained in an experimentwith rats fed a proanthocyanidin-rich cocoa preparation [67]where the authors found a significant decrease in the propor-tion of Bacteroides Clostridium and Staphylococcus generain the feces of cocoa-fed animals Interestingly reductions inClostridium species were found to correlate with weight lossand decrease in body mass index

Larrosa et al [68] observed an increase in lactobacilliand bifidobacteria when resveratrol (3541015840-trihydroxy-trans-stilbene) which naturally occurs in grapes and grape-derivedfoodstuffs such as red wine was administered to rats Afterinduction of colitis by dextran sulphate sodium proliferationof both E coli and enterobacteria was lower in rats treatedwith resveratrol than in control rats This could be the resultof an indirect effect of resveratrol-supplemented diet whichincreased bifidobacteria and lactobacilli counts preventingthe colonization and invasion of tissues by enterobacteriaincluding E coli

Prebiotic activity of wild blackcurrant extracts observedin in vitro experiments was further confirmed in rats byMolan et al [69] A significant increase in the populationsize of lactobacilli and bifidobacteria was observed after dailyadministration of those extracts to rats Similarly a grapeantioxidant dietary fibre preparation was found to increasethe population of Lactobacillus spp when fed to rats whereaspopulations of Bifidobacterium spp decreased and changes inE coli and Bacteroides vulgatus counts were not significant[50]

Recently Lacombe et al [70] studied the composition andfunctional potential of the colon microbiota from rats feda diet enriched in lowbush wild blueberries Application ofnovel metagenomic techniques (Illumina shotgun sequenc-ing) revealed a significant reduction in the relative abundanceof the genera Lactobacillus and Enterococcus associated withwild blueberries intake In addition hierarchical analysisshowed a significant increase in the relative abundanceof the phylum Actinobacteria the order Actinomycetalesand several novel genera under the family Bifidobacteri-aceae and Coriobacteriaceae in the blueberries group Theauthors indicated that although the microbiome of ratsdiffers from humans the applied model was a powerfultool to study population dynamics and related metabolicfunctions Metagenomic studies can determine microbialcommunity profiles gene presenceabsence and abundanceand functional repertoire however they can only infer an

observed phenotype since a gene presence does not imply itsexpression or functionality [71]

7 Human Intervention Studies

Investigations involving the use of humans potentially pro-vide the best models for studying the interactions of foodcomponents (eg polyphenols) with microbiota although invivo intervention trials hold inevitable practical and ethicallimitations [12] The use of cross-over designs where volun-teers serve as their own control permits multilevel analysisschemes that increase power but requires a relevant numberof volunteers to allow for statistically significant multivariatemodels [72] Up to now only a few studies have examinedthe in vivo impact of dietary polyphenols on the humangut microbiota and most of them were focused on singlepolyphenol molecules and selected bacterial populations Asummary of human intervention studies about effects ofpolyphenols in the modulation of the intestinal microbiotais collected in Table 4 In these studies the polyphenol doseused was much dependent on the type of food preparationand its concentration normally ranging from 01 to 4 thetreatment time was also variable from 10 days to 2 monthsand the applied microbial techniques were diverse (platecount DGGE FISH T-RFLP and qPCR)

In a study with a reduced number of subjects (119899 =8) Okubo et al [73] reported a notably increase in thepercentages of Bifidobacterium spp in total fecal countsafter an intervention with a product containing 70 of teapolyphenols A significant decrease of C perfringens andother Clostridium spp was also observed during the intakeperiod However in a crossover feeding study (number ofvolunteers not reported) that investigated the effects of blacktea drinking on hypercholesterolemic volunteers Mai et al[74] found that although specific bacterial groups were notaffected the total amount of bacteria significantly decreasedhighlighting large interindividual variations More recentlyan intervention study (119899 = 10) by Jin et al [75] confirmedan overall tendency for the proportion of bifidobacteria toincrease because of green tea consumption even thoughthere were interindividual differences in the Bifidobacteriumspecies

Yamakoshi et al [76] showed that administration of aproanthocyanidin-rich extract from grape seeds to healthyvolunteers (119899 = 9) significantly increased the fecal number ofBifidobacterium whereas the number of putrefactive bacteriasuch as enterobacteria tended to decrease The interactionbetween proanthocyanidins and intestinal bacteria was alsoconfirmed in a randomized double-blind crossover andcontrolled intervention study (119899 = 22) ingesting two cocoadrinks exhibiting low and high polyphenol content [77]Compared with the consumption of the low-flavan-3-olcocoa drink the daily consumption of the high-flavan-3-ol cocoa drink significantly increased the bifidobacteria andlactobacilli populations but significantly decreased clostridiacounts

Queipo-Ortuno et al [78] performed a randomizedcrossover and controlled trial (119899 = 10) consisting of theintake of red wine dealcoholized red wine and gin over

BioMed Research International 9

Table4Hum

aninterventio

nstu

dies

Reference

Volunteer

number

Phenolic

compo

undfood

Dose

Treatm

ent

duratio

nMicrobial

techniqu

ePo

pulatio

nincrease

Popu

latio

ndecrease

Noeffect

Oku

boetal

(1994)[73]

8Green

tea

(Sun

phenon

)04g

3tim

esper

day

4weeks

Platec

ount

Cperfr

ingens

Clostridium

spp

Yamakoshi

etal(2001)[76]

9Proantocyanidin-

richextractfrom

grapes

eeds

05g

day

6weeks

Platec

ount

Bifid

obacteriu

mspp

Enterobacteriaceae

Maietal

(200

4)[74]

15Blacktea

700m

gteas

olids5

times

perd

ay21

days

FISH

DGGE

Totalbacteria

Nochanges

Claveletal

(2005)

[83]

39Isofl

avon

es100m

gday

2mon

ths

TTGEFISH

Ccoccoides-E

rectale

grou

pBifid

obacteriu

mspp

Lactobacillus-

Enterococcus

spp

Faecalibacteriu

mprau

snitziisubgroup

Costabileetal

(2008)

[84]

31Who

legrainwheat

cereals

48gday

3weeks

FISH

Bifid

obacteria

Lactob

acilli

Totalbacteria

Bacteroidesspp

C

histo

lyticum

perfringens

grou

pAc

etobacteriu

mspp

Jaqu

etetal

(200

9)[87]

16Coff

ee3cupsday

3weeks

FISH

DGGE

Bifid

obacteriu

mspp

Carvalho

-Wellsetal

(2010)

[85]

32Who

legrainmaize

cereals

48gday

3weeks

FISH

Bifid

obacteria

Totalbacteria

Bacteroidesspp

C

histo

lyticum

perfringens

grou

pAc

etobacteriu

mspp

Gill

etal

(2010)

[80]

10Ra

spberrypu

ree

20gday

4days

PCR-DGGE

Nochangesinthep

rofileo

fcolonicb

acteria

Shinoh

arae

tal(2010)[79]

8Ap

ples

2applesday

2weeks

Platec

ount

Lactobacillus

spp

Streptococcusspp

En

terococcus

spp

Enterobacteriaceae

lecithinase-po

sitive

clostrid

iainclu

ding

Cperfr

ingens

Pseudomonas

spp

10 BioMed Research International

Table4Con

tinued

Reference

Volunteer

number

Phenolic

compo

undfood

Dose

Treatm

ent

duratio

nMicrobial

techniqu

ePo

pulatio

nincrease

Popu

latio

ndecrease

Noeffect

Tzou

nise

tal

(2011)[77]

22Cocoa

flavano

l494m

gday

29mgday

4weeks

FISH

Bifid

obacteriu

mspp

Lactobacillus

spp

Chisto

lyticum

perfringens

grou

p

Vend

ramee

tal(2011)[81]

15Wild

blueberry

drink

25gwild

blueberriesd

ay6weeks

qPCR

Bifid

obacteriu

mspp

Lacidophilus

Bacteroidesspp

Prevotellaspp

Enterococcus

spp

Ccoccoides

Queipo-

Ortun

oetal

(2012)

[78]

10Re

dwine

272m

Lday

20days

qPCR

Enterococcus

spp

Prevotellaspp

Bacteroides

Bifid

obacteriu

mspp

Bacteroidesu

niform

isEggerthella

lenta

Blautia

coccoides-E

rectaleg

roup

Clostridium

spp

Chisto

lyticum

group

Actin

obacteria

Jinetal(2012)

[75]

10Green

tea

1000

mLday

10days

T-RF

LPqP

CRBifid

obacteriu

mspp

Gug

lielm

ettiet

al(2013)[82]

15Wild

blueberries

drink

25gwild

blueberriesd

ay6weeks

qPCR

Blongum

subspinfantis

Cuervo

etal

(2014)

[86]

38

Dairy

prod

ucts

Fruits

Vegetables

Cereals

Food

intake

was

recorded

usingan

annu

alfood

frequ

ency

questio

nnaire

qPCR

Lactobacillus

Bcoccoides

Clep

tum

BioMed Research International 11

three consecutive periods After the red wine period thebacterial concentrations of proteobacteria fusobacteria Fir-micutes and Bacteroidetes markedly increased comparedwith the washout period significant increases in the num-ber of Bifidobacterium spp and Prevotella spp were alsoobserved However Lactobacillus spp Clostridium spp andC histolyticum group concentrations remained unchangedthroughout the study

In a small-scale observational study (119899 = 8) Shinoharaet al [79] found that the number of bifidobacteria in fecessignificantly increased during apple intake and the numbersof Lactobacillus spp Streptococcus spp and Enterococcusspp tended to increase On the contrary enterobacteriaand lecithinase-positive clostridia including C perfringensand Pseudomonas species tended to decrease Howeverthat study did not use culture-independent microbiologytechniques and suffered from the lack of a control groupAlso in relation to fruits another small human interventionstudy (119899 = 10) with raspberry puree [80] did not observestatistically significant alterations in the profile of colonicbacteria probably due to high interindividual variation infecal bacteria although the profiles of microbial metabolitesof raspberry polyphenols varied greatly between individualsindicating that the type of gut microbiota affects cataboliteprofiles released by bacteria in the colonThis lack of effect onthe intestinal microbiota after the intake of raspberry pureemight also be due to the short duration of the treatment aswell as the techniques employed to quantify the intestinalmicrobiota

Vendrame et al [81] studied the potential prebioticactivity of a drink elaborated fromwild blueberries especiallyrich in anthocyanins in a small intervention trial (119899 = 15) Asignificant increase in Bifidobacterium spp and L acidophilusgroup was detected while no significant differences wereobserved for Bacteroides spp Prevotella spp Enterococcusspp and C coccoides In a further paper of the same group[82] seven different intragenus bifidobacteria taxonomicclusters that were among the most common and abundantbifidobacteria species inhabiting the human gutwere targetedin the same samples It was found thatB adolescentisB breveB catenulatumpseudocatenulatum and B longum subsplongumwere always present in the group of subjects enrolledwhereas B bifidum and B longum subsp infantis were notIn spite of the large interindividual variability a significantincrease of B longum subsp infantis cell concentration wasobserved in the feces of volunteers after the wild blueberrydrink treatment which was attributed to the presence ofprebiotic (bifidogenic) molecules from blueberries possiblyfibers and glycosylated anthocyanins

In a study with postmenopausal women (119899 = 39)Clavel et al [83] found that isoflavone supplementationstimulated dominant microorganisms of the C coccoides-Erectale cluster Lactobacillus-Enterococcus group Faecalibac-terium prausnitzii subgroup and Bifidobacterium genus Itwas also suggested that the concentration of C coccoides-Erectale cluster was related to women capacity to excrete equolan intestinal metabolite from daidzein In two interventionstudies with whole grain breakfast cereals from wheat (119899 =31) and maize (119899 = 32) [84 85] the ingestion of both

products resulted in significant increases in fecal bifidobac-teria andor lactobacilli without changing the relative abun-dance of other dominant members of the gut microbiotaLittle or no changes were observed in the numbers of totalbacteria Bacteroides spp C histolyticumperfringens groupand Acetobacterium spp present in the feces However aswhole grains are good sources of dietary fiber it is difficult toascribe the observed effects only to the phenolic compoundspresent in these foods In this respect Cuervo et al [86] haverecently studied the correlations between the intake of fiberand polyphenols from diet and fecal microbiota compositionin a cohort of apparently healthy subjects Results showedthat the intake of soluble pectins and flavanones fromorangespresented a negative correlation with the levels of B coccoidesand C leptum By contrast the intake of white breadproviding hemicellulose and resistant starch was directlycorrelated with Lactobacillus

Finally another human trial (119899 = 16) carried out byJaquet et al [87] assessed the impact of a moderate con-sumption of instant coffee on the general composition ofthe human intestinal bacterial population Coffee bever-ages contain significant amounts of soluble fibre (mainlygalactomannans and arabinogalactan-proteins) and phenoliccompounds (chlorogenic acids) which arewell utilised by thehuman fecal microbiota It was observed that although fecalprofiles of the dominant microbiota were not significantlyaffected after the consumption of the coffee the populationof Bifidobacterium spp increased being the largest increaseobserved for those volunteers showing the lowest initialbifidobacteria levels

8 Conclusions

This review has tried to summarize the current knowledgein relation to the phenolic metabolism by gut microbiota andthemodulation of the gutmicrobiota by phenolic compoundsand polyphenol-rich dietary sourcesThere are evidences thatthe beneficial effects attribute to dietary polyphenols dependon their biotransformation by the gut microbiota Thereforeit is important to investigate the bacterial species impli-cated in the metabolism of dietary polyphenols and furtherresearch is still needed in relation to the resultant microbialmetabolites to ascertain their mechanisms of action Onthe other hand a great number of in vitro and in vivo (inanimals andhumans) studies showing the influence of dietarypolyphenols on gut-inhabiting bacteria have been publishedin recent years Although in vitro assays facilitate experimen-tation caution must be taken in extrapolating results to invivo situation as many factors are acting upon this processIn general in both in vitro and in vivo studies polyphenols orpolyphenol-rich sources have shown to influence the relativeabundance of different bacterial groups within the gut micro-biota reducing numbers of potential pathogens including Cperfringens and C histolyticum and certain Gram-negativeBacteroides spp and enhancing mainly beneficial Clostridiabifidobacteria and lactobacilli A better understanding of theinteraction between dietary polyphenols and gut microbiotathrough the emerging advances in high-throughput meta-genomic transcriptomic and proteomic approaches would

12 BioMed Research International

be essential in order to identify genes and micro-organismsinvolved in polyphenol (in)activation and conversion andthus to elucidate the implications of diet on the modulationof microbiota for delivering health benefits

Functional foods are considered to enhance the protectiveeffects against diseases derived from some food componentsIn the last decades dairy fermented foods have probablybeen one of the most-developed functional products andhave deserved intensive research In this expansion dairyfermented foods have been supplemented with fruits cerealsand other stuffs of plant origin all of which represent a highpercentage of the current market of the dairy industry Theseproducts have a healthy appeal which attracts consumersThus fruit juicesconcentrates and prepared fruits (in theform of pieces pulp and even flour) have been successfullyincorporated in dairy fermented foods as sources of prebioticfibers and phytochemicals Among these phytochemicalspresent in plant-derived foods polyphenols have gainedmuch interest due to their diverse potential beneficial effectsin human health The supplementation of dairy fermentedproducts with rich-polyphenolic stuffs (phenolic extractsphenolic-enriched fractions etc) seems to be an effectivetechnological option to improve the benefits of these productsin the balance of the intestinal microbiota due not only to theaction of the probiotics but also to the potential modulationeffects exerted by polyphenols as it has been described in thisreview Further research in this area will aim to accomplishthe benefits of both probiotic strains and polyphenols inrelation to gut health

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors of this review were funded by the SpanishMINECO through different projects (AGL2012-40172-C02-01 AGL2010-17499 and BFU2012-35228) and the CON-SOLIDER INGENIO 2010 programme (project FUN-C-FOOD CSD2007-063) as well as Comunidad de Madrid(project ALIBIRD P2009AGR-1469) Montserrat Duenaswould like to thank the Spanish ldquoRamon y Cajalrdquo Programmefor a contract

References

[1] S E Power P W OrsquoToole C Stanton R P Ross and GF Fitzgerald ldquoIntestinal microbiota diet and healthrdquo BritishJournal of Nutrition vol 111 no 3 pp 387ndash402 2014

[2] PDeCruz L Prideaux JWagner et al ldquoCharacterization of thegastrointestinal microbiota in health and inflammatory boweldiseaserdquo Inflammatory Bowel Diseases vol 18 no 2 pp 372ndash390 2012

[3] A Kramer S Bekeschus B M Broker H Schleibinger BRazavi and O Assadian ldquoMaintaining health by balancingmicrobial exposure and prevention of infection the hygienehypothesis versus the hypothesis of early immune challengerdquoJournal of Hospital Infection vol 83 no 1 pp S29ndashS34 2013

[4] M Rescigno ldquoIntestinal microbiota and its effects on theimmune systemrdquo Cellular Microbiology vol 16 no 7 pp 1004ndash1013 2014

[5] M G L Hertog E J M Feskens P C H HollmanM B Katanand D Kromhout ldquoDietary antioxidant flavonoids and risk ofcoronary heart disease the Zutphen Elderly StudyrdquoThe Lancetvol 342 no 8878 pp 1007ndash1011 1993

[6] I C W Arts and P C H Hollman ldquoPolyphenols and diseaserisk in epidemiologic studiesrdquoThe American Journal of ClinicalNutrition vol 81 no 1 pp 317Sndash325S 2009

[7] D del Rio A Rodriguez-Mateos J P E Spencer M TognoliniG Borges and A Crozier ldquoDietary (poly)phenolics in humanhealth structures bioavailability and evidence of protectiveeffects against chronic diseasesrdquo Antioxidants amp Redox Signal-ing vol 18 no 14 pp 1818ndash1892 2013

[8] F Perez-Vizcaino and J Duarte ldquoFlavonols and cardiovasculardiseaserdquo Molecular Aspects of Medicine vol 31 no 6 pp 478ndash494 2010

[9] J P E Spencer K Vafeiadou R J Williams and D VauzourldquoNeuroinflammation modulation by flavonoids and mecha-nisms of actionrdquo Molecular Aspects of Medicine vol 33 no 1pp 83ndash97 2012

[10] J M Laparra and Y Sanz ldquoInteractions of gut microbiota withfunctional food components and nutraceuticalsrdquo Pharmacolog-ical Research vol 61 no 3 pp 219ndash225 2010

[11] X He M L Marco and C M Slupsky ldquoEmerging aspects offood and nutrition on gut microbiotardquo Journal of Agriculturaland Food Chemistry vol 61 no 40 pp 9559ndash9574 2013

[12] D Hervert-Hernandez and I Goni ldquoDietary polyphenols andhuman gut microbiota a reviewrdquo Food Reviews Internationalvol 27 no 2 pp 154ndash169 2011

[13] K M Tuohy L Conterno M Gasperotti and R Viola ldquoUp-regulating the human intestinal microbiome using whole plantfoods polyphenols andor fiberrdquo Journal of Agricultural andFood Chemistry vol 60 no 36 pp 8776ndash8782 2012

[14] U Etxeberria A Fernandez-Quintela F I Milagro L AguirreJ A Martınez and M P Portillo ldquoImpact of polyphenols andpolyphenol-rich dietary sources on gut microbiota composi-tionrdquo Journal of Agricultural and Food Chemistry vol 61 no 40pp 9517ndash9533 2013

[15] F Cardona C Andres-Lacueva S Tulipani F J Tinahonesand M I Queipo-Ortuno ldquoBenefits of polyphenols on gutmicrobiota and implications in human healthrdquo Journal ofNutritional Biochemistry vol 24 no 8 pp 1415ndash1422 2013

[16] M V Selma J C Espın and F A Tomas-Barberan ldquoInteractionbetween phenolics and gut microbiota role in human healthrdquoJournal of Agricultural and Food Chemistry vol 57 no 15 pp6485ndash6501 2009

[17] T RequenaMMonagasM A Pozo-Bayon et al ldquoPerspectivesof the potential implications ofwine polyphenols on humanoraland gut microbiotardquo Trends in Food Science amp Technology vol21 no 7 pp 332ndash344 2010

[18] J Van Duynhoven E E Vaughan F van Dorsten et alldquoInteractions of black tea polyphenols with human gut micro-biota implications for gut and cardiovascular health1-4rdquo TheAmerican Journal of Clinical Nutrition vol 98 no 6 pp 1631Sndash1641S 2013

[19] SMoco F-P JMartin and S Rezzi ldquoMetabolomics view on gutmicrobiome modulation by polyphenol-rich foodsrdquo Journal ofProteome Research vol 11 no 10 pp 4781ndash4790 2012

BioMed Research International 13

[20] R K Buddington and P T Sangild ldquoCompanion animalssymposium development of the mammalian gastrointestinaltract the resident microbiota and the role of diet in early liferdquoJournal of Animal Science vol 89 no 5 pp 1506ndash1519 2011

[21] K Tiihonen A C Ouwehand and N Rautonen ldquoHumanintestinal microbiota and healthy ageingrdquo Ageing ResearchReviews vol 9 no 2 pp 107ndash116 2010

[22] D Mariat O Firmesse F Levenez et al ldquoThe firmicutesbacteroidetes ratio of the human microbiota changes with agerdquoBMCMicrobiology vol 9 article 123 2009

[23] M Arumugam J Raes E Pelletier et al ldquoEnterotypes of thehuman gutmicrobiomerdquoNature vol 473 no 7346 pp 174ndash1802011

[24] G D Wu J Chen C Hoffmann et al ldquoLinking long-termdietary patterns with gut microbial enterotypesrdquo Science vol334 no 6052 pp 105ndash108 2011

[25] I B JefferyM J Claesson PWOrsquoToole and F Shanahan ldquoCat-egorization of the gut microbiota enterotypes or gradientsrdquoNature Reviews Microbiology vol 10 no 9 pp 591ndash592 2012

[26] WM de Vos andM Nieuwdorp ldquoGenomics a gut predictionrdquoNature vol 498 no 7452 pp 48ndash49 2013

[27] P B Eckburg E M Bik C N Bernstein et al ldquoMicrobiologydiversity of the human intestinal microbial florardquo Science vol308 no 5728 pp 1635ndash1638 2005

[28] E G Zoetendal C T Collier S Koike R I Mackie and H RGaskins ldquoMolecular ecological analysis of the gastrointestinalmicrobiota a reviewrdquo Journal of Nutrition vol 134 no 2 pp465ndash472 2004

[29] M H Fraher PW OrsquoToole and E MM Quigley ldquoTechniquesused to characterize the gut microbiota a guide for the clini-cianrdquo Nature Reviews Gastroenterology and Hepatology vol 9no 6 pp 312ndash322 2012

[30] R A Kemperman S Bolca L C Roger and E E VaughanldquoNovel approaches for analysing gut microbes and dietarypolyphenols challenges and opportunitiesrdquo Microbiology vol156 no 11 pp 3224ndash3231 2010

[31] R A Kemperman G Gross S Mondot et al ldquoImpact ofpolyphenols from black tea and red winegrape juice on a gutmodel microbiomerdquo Food Research International vol 53 no 2pp 659ndash669 2013

[32] M N Clifford ldquoDiet-derived phenols in plasma and tissues andtheir implications for healthrdquo Planta Medica vol 70 no 12 pp1103ndash1114 2004

[33] A Crozier D del Rio and M N Clifford ldquoBioavailability ofdietary flavonoids and phenolic compoundsrdquoMolecular Aspectsof Medicine vol 31 no 6 pp 446ndash467 2010

[34] A J Day M S Dupont S Ridley et al ldquoDeglycosylation offlavonoid and isoflavonoid glycosides by human small intestineand liver beta-glucosidase activityrdquo FEBS Letters vol 436 no 1pp 71ndash75 1998

[35] A J Day F J Canada J C Dıaz et al ldquoDietary flavonoid andisoflavone glycosides are hydrolysed by the lactase site of lactasephlorizin hydrolaserdquo FEBS Letters vol 468 no 2-3 pp 166ndash1702000

[36] A Scalbert and G Williamson ldquoDietary intake and bioavail-ability of polyphenolsrdquo Journal of Nutrition vol 130 no 8 pp2073Sndash2085S 2000

[37] A R Rechner G Kuhnle H Hu et al ldquoThe metabolism ofdietary polyphenols and the relevance to circulating levels ofconjugated metabolitesrdquo Free Radical Research vol 36 no 11pp 1229ndash1241 2002

[38] A-M Aura K A OrsquoLeary G Williamson et al ldquoQuercetinderivatives are deconjugated and converted to hydroxypheny-lacetic acids but not methylated by human fecal flora in vitrordquoJournal of Agricultural and Food Chemistry vol 50 no 6 pp1725ndash1730 2002

[39] A-M Aura ldquoMicrobial metabolism of dietary phenolic com-pounds in the colonrdquo Phytochemistry Reviews vol 7 no 3 pp407ndash429 2008

[40] M Monagas M Urpi-Sarda F Sanchez-Patan et al ldquoInsightsinto themetabolism andmicrobial biotransformation of dietaryflavan-3-ols and the bioactivity of their metabolitesrdquo Food andFunction vol 1 no 3 pp 233ndash253 2010

[41] GWilliamson andMNClifford ldquoColonicmetabolites of berrypolyphenols the missing link to biological activityrdquo BritishJournal of Nutrition vol 104 no 3 pp S48ndashS66 2010

[42] D M Jacobs E Gaudier J van Duynhoven and E E VaughanldquoNon-digestible food ingredients colonic microbiota and theimpact on gut health and immunity a role for metabolomicsrdquoCurrent Drug Metabolism vol 10 no 1 pp 41ndash54 2009

[43] S Bolca S Possemiers V Maervoet et al ldquoMicrobial anddietary factors associatedwith the 8-prenylnaringenin producerphenotype a dietary intervention trial with fifty healthy post-menopausal Caucasian womenrdquo British Journal of Nutritionvol 98 no 5 pp 950ndash959 2007

[44] X Tzounis J Vulevic G G C Kuhnle et al ldquoFlavanolmonomer-induced changes to the human faecal microflorardquoBritish Journal of Nutrition vol 99 no 4 pp 782ndash792 2008

[45] M Hidalgo M J Oruna-Concha S Kolida et al ldquoMetabolismof anthocyanins by human gut microflora and their influenceon gut bacterial growthrdquo Journal of Agricultural and FoodChemistry vol 60 no 15 pp 3882ndash3890 2012

[46] A L Molan M A Lila J Mawson and S De ldquoIn vitroand in vivo evaluation of the prebiotic activity of water-soluble blueberry extractsrdquo World Journal of Microbiology andBiotechnology vol 25 no 7 pp 1243ndash1249 2009

[47] D Bialonska P Ramnani S G Kasimsetty K R Muntha GR Gibson and D Ferreira ldquoThe influence of pomegranate by-product and punicalagins on selected groups of human intesti-nal microbiotardquo International Journal of FoodMicrobiology vol140 no 2-3 pp 175ndash182 2010

[48] G Mandalari R M Faulks C Bisignano K W Waldron ANarbad and M S J Wickham ldquoIn vitro evaluation of theprebiotic properties of almond skins (Amygdalus communisL)rdquoFEMS Microbiology Letters vol 304 no 2 pp 116ndash122 2010

[49] V Fogliano M L Corollaro P Vitaglione et al ldquoIn vitro bioac-cessibility and gut biotransformation of polyphenols present inthe water-insoluble cocoa fractionrdquoMolecular Nutritionamp FoodResearch vol 55 supplement 1 pp S44ndashS55 2011

[50] M J Pozuelo A Agis-Torres D Hervert-Hernandez etal ldquoGrape antioxidant dietary fiber stimulates Lactobacillusgrowth in rat cecumrdquo Journal of Food Science vol 77 no 2 ppH59ndashH62 2012

[51] C Cueva F Sanchez-Patan M Monagas et al ldquoIn vitrofermentation of grape seed flavan-3-ol fractions by humanfaecal microbiota changes in microbial groups and phenolicmetabolitesrdquo FEMSMicrobiology Ecology vol 83 no 3 pp 792ndash805 2013

[52] F Sanchez-Patan C CuevaMMonagas et al ldquoIn vitro fermen-tation of a red wine extract by human gut microbiota changesin microbial groups and formation of phenolic metabolitesrdquoJournal of Agricultural and Food Chemistry vol 60 no 9 pp2136ndash2147 2012

14 BioMed Research International

[53] E Barroso F Sanchez-Patan P J Martın-Alvarez et al ldquoLacto-bacillus plantarum IFPL935 favors the initial metabolism of redwine polyphenols when added to a colonic microbiotardquo Journalof Agricultural and Food Chemistry vol 61 no 42 pp 10163ndash10172 2013

[54] G R Gibson J H Cummings and G T Macfarlane ldquoUse ofa three-stage continuous culture system to study the effect ofmucin on dissimilatory sulfate reduction and methanogenesisby mixed populations of human gut bacteriardquo Applied andEnvironmentalMicrobiology vol 54 no 11 pp 2750ndash2755 1988

[55] KMollyMVandeWoestyne andWVerstraete ldquoDevelopmentof a 5-step multi-chamber reactor as a simulation of thehuman intestinal microbial ecosystemrdquo Applied Microbiologyand Biotechnology vol 39 no 2 pp 254ndash258 1993

[56] M Minekus M Smeets-Peeters A Bernalier et al ldquoAcomputer-controlled system to simulate conditions of thelarge intestine with peristaltic mixing water absorption andabsorption of fermentation productsrdquoAppliedMicrobiology andBiotechnology vol 53 no 1 pp 108ndash114 1999

[57] PDeBoever BDeplancke andWVerstraete ldquoFermentation bygut microbiota cultured in a simulator of the human intestinalmicrobial ecosystem is improved by supplementing a soygermpowderrdquo Journal of Nutrition vol 130 no 10 pp 2599ndash26062000

[58] C S Yang X Wang G Lu and S C Picinich ldquoCancerprevention by tea animal studies molecular mechanisms andhuman relevancerdquoNature Reviews Cancer vol 9 no 6 pp 429ndash439 2009

[59] R E Ley F Backhed P Turnbaugh C A Lozupone R DKnight and J I Gordon ldquoObesity alters gut microbial ecologyrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 102 no 31 pp 11070ndash11075 2005

[60] H Hara N Orita S Hatano et al ldquoEffect of tea polyphenols onfecal flora and fecal metabolic products of pigsrdquo The Journal ofVeterinary Medical Science vol 57 no 1 pp 45ndash49 1995

[61] N Ishihara D-C Chu S Akachi and L R Juneja ldquoImprove-ment of intestinal microflora balance and prevention of diges-tive and respiratory organ diseases in calves by green teaextractsrdquo Livestock Production Science vol 68 no 2-3 pp 217ndash229 2001

[62] P Dolara C Luceri C De Filippo et al ldquoRed wine polyphenolsinfluence carcinogenesis intestinal microflora oxidative dam-age and gene expression profiles of colonicmucosa in F344 ratsrdquoMutation Research-Fundamental and Molecular Mechanisms ofMutagenesis vol 591 no 1-2 pp 237ndash246 2005

[63] S Sembries G Dongowski K Mehrlander F Will and HDietrich ldquoPhysiological effects of extraction juices from applegrape and red beet pomaces in ratsrdquo Journal of Agricultural andFood Chemistry vol 54 no 26 pp 10269ndash10280 2006

[64] S Sembries G Dongowski G Jacobasch K Mehrlander FWill andH Dietrich ldquoEffects of dietary fibre-rich juice colloidsfrom apple pomace extraction juices on intestinal fermentationproducts and microbiota in ratsrdquo British Journal of Nutritionvol 90 no 3 pp 607ndash615 2003

[65] A Viveros S Chamorro M Pizarro I Arija C Centeno andA Brenes ldquoEffects of dietary polyphenol-rich grape productson intestinal microflora and gut morphology in broiler chicksrdquoPoultry Science vol 90 no 3 pp 566ndash578 2011

[66] A H Smith and R I Mackie ldquoEffect of condensed tannins onbacterial diversity andmetabolic activity in the rat gastrointesti-nal tractrdquo Applied and Environmental Microbiology vol 70 no2 pp 1104ndash1115 2004

[67] M Massot-Cladera T Perez-Berezo A Franch M Castelland F J Perez-Cano ldquoCocoa modulatory effect on rat faecalmicrobiota and colonic crosstalkrdquo Archives of Biochemistry andBiophysics vol 527 no 2 pp 105ndash112 2012

[68] M Larrosa M J Yanez-Gascon M V Selma et al ldquoEffectof a low dose of dietary resveratrol on colon microbiotainflammation and tissue damage in a DSS-induced colitis ratmodelrdquo Journal of Agricultural and Food Chemistry vol 57 no6 pp 2211ndash2220 2009

[69] A-L Molan Z Liu andM Kruger ldquoThe ability of blackcurrantextracts to positively modulate key markers of gastrointestinalfunction in ratsrdquoWorld Journal ofMicrobiologyampBiotechnologyvol 26 no 10 pp 1735ndash1743 2010

[70] A Lacombe R W Li D Klimis-Zacas et al ldquoLowbush wildblueberries have the potential to modify gut microbiota andxenobiotic metabolism in the rat colonrdquo PLoS ONE vol 8 no6 Article ID e67497 2013

[71] R Saad M R Rizkallah and R K Aziz ldquoGut Pharmacomicro-biomics the tip of an iceberg of complex interactions betweendrugs and gut-associated microbesrdquo Gut Pathogens vol 4 no1 article 16 2012

[72] E J J Van Velzen J A Westerhuis J P M van Duynhovenet al ldquoMultilevel data analysis of a crossover designed humannutritional intervention studyrdquo Journal of Proteome Researchvol 7 no 10 pp 4483ndash4491 2008

[73] T Okubo N Ishihara H Takahashi et al ldquoEffects of partiallyhydrolyzed guar gum intake on human intestinal microfloraand itsmetabolismrdquoBioscience Biotechnology andBiochemistryvol 58 no 8 pp 1364ndash1369 1994

[74] V Mai H A Katki H Harmsen et al ldquoEffects of a controlleddiet and black tea drinking on the fecalmicroflora compositionand the fecal bile acid profile of human volunteers in a double-blinded ramdomized feeding studyrdquo The Journal of Nutritionvol 134 no 2 pp 473ndash478 2004

[75] J-S Jin M Touyama T Hisada and Y Benno ldquoEffectsof green tea consumption on human fecal microbiota withspecial reference to Bifidobacterium speciesrdquoMicrobiology andImmunology vol 56 no 11 pp 729ndash739 2012

[76] J Yamakoshi S Tokutake M Kikuchi Y Kubota H Konishiand T Mitsuoka ldquoEffect of proantocyanidin -rich extract fromgrape seed on human fecal flora and fecalodorrdquo FASEB Journalvol 15 no 4 p A633 2001

[77] X Tzounis A Rodriguez-Mateos J Vulevic G R Gibson CKwik-Uribe and J P E Spencer ldquoPrebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomizedcontrolled double-blind crossover intervention studyrdquo TheAmerican Journal of Clinical Nutrition vol 93 no 1 pp 62ndash722011

[78] M I Queipo-Ortuno M Boto-Ordonez M Murri et alldquoInfluence of red wine polyphenols and ethanol on the gutmicrobiota ecology and biochemical biomarkersrdquo AmericanJournal of Clinical Nutrition vol 95 no 6 pp 1323ndash1334 2012

[79] K Shinohara Y Ohashi K Kawasumi A Terada and TFujisawa ldquoEffect of apple intake on fecal microbiota andmetabolites in humansrdquo Anaerobe vol 16 no 5 pp 510ndash5152010

[80] C I R Gill G J Mcdougall S Glidewell et al ldquoProfiling ofphenols in human fecal water after raspberry supplementationrdquoJournal of Agricultural and Food Chemistry vol 58 no 19 pp10389ndash10395 2010

[81] S Vendrame S Guglielmetti P Riso S Arioli D Klimis-Zacasand M Porrini ldquoSix-week consumption of a wild blueberry

BioMed Research International 15

powder drink increases Bifidobacteria in the human gutrdquoJournal of Agricultural and Food Chemistry vol 59 no 24 pp12815ndash12820 2011

[82] S Guglielmetti D Fracassetti V Taverniti et al ldquoDifferentialmodulation of human intestinal Bifidobacterium populationsafter consumption of a wild blueberry (Vaccinium angusti-folium) drinkrdquo Journal of Agricultural and Food Chemistry vol61 no 34 pp 8134ndash8140 2013

[83] T Clavel M Fallani P Lepage et al ldquoIsoflavones and func-tional foods alter the dominant intestinal microbiota in post-menopausal womenrdquo Journal of Nutrition vol 135 no 12 pp2786ndash2792 2005

[84] A Costabile A Klinder F Fava et al ldquoWhole-grain wheatbreakfast cereal has a prebiotic effect on the human gut micro-biota a double-blind placebo-controlled crossover studyrdquoBritish Journal of Nutrition vol 99 no 1 pp 110ndash120 2008

[85] A L Carvalho-Wells K Helmolz C Nodet et al ldquoDetermina-tion of the in vivo prebiotic potential of a maize-based wholegrain breakfast cereal a human feeding studyrdquo British Journalof Nutrition vol 104 no 9 pp 1353ndash1356 2010

[86] A Cuervo L Valdes N Salazar et al ldquoPilot study of diet andmicrobiota interactive associations of fibers and polyphenolswith human intestinal bacteriardquo Journal of Agricultural andFood Chemistry vol 62 no 23 pp 5330ndash5336 2014

[87] M Jaquet I Rochat J Moulin C Cavin and R BibilonildquoImpact of coffee consumption on the gut microbiota a humanvolunteer studyrdquo International Journal of FoodMicrobiology vol130 no 2 pp 117ndash121 2009

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Page 6: Review Article A Survey of Modulation of Gut Microbiota by ...downloads.hindawi.com/journals/bmri/2015/850902.pdf · Review Article A Survey of Modulation of Gut Microbiota by Dietary

6 BioMed Research International

Table 2 Studies using the gastrointestinal simulators (ie SHIME)

Reference Simulator Phenoliccompoundfood Dose Time Microbial

techniquePopulationincrease Population decrease

De Boeveret al (2000)[57]

SHIME Soy germ powder 25 gday 2 weeks Plate count

EnterobacteriaceaeColiforms

Lactobacillus sppStaphylococcus sppClostridium spp

Kempermanet al (2013)[31]

Twin-SHIME Black tea extract

3 times dailydosing(1000mg

polyphenolsas total daily

dose)

2 weeks

Plate countqPCR

PCR-DGGEpyrosequencing

Klebsiella sppEnterococci

Akkermansia spp

BifidobacteriaBlautia coccoidesAnaeroglobus sppVictivallis spp

Kempermanet al (2013)[31]

Twin-SHIME

Red wine-grapeextract

3 times dailydosing(1000mg

polyphenolsas total daily

dose)

2 weeks

Plate countqPCR

PCR-DGGEpyrosequencing

Klebsiella sppAlistipes spp

Cloacibacillus sppVictivallis spp

Akkermansia spp

BifidobacteriaBlautia coccoides

groupAnaeroglobus spp

Subdoligranulum sppBacteroides

5 Studies Using HumanGastrointestinal Simulators

In contrast to short-duration experiments with static gutmodels longer-term experiments are required when theadaptation of the gut microbial community to dietarypolyphenols needs to be assessed To this end dynamic invitro gut models such as the ldquoReadingrdquo model [54] theSimulator of the Human Intestinal Microbial Ecosystem(SHIME) the TNO Intestinal Model 2 (TIM2) [55 56] andthe recent gastrointestinal simulator set up in our Institute(SIMGI) (unpublished work) have been developed where gutmicrobiota are cultured over a longer time frame (days toweeks) in one or multiple connected pH controlled vesselsrepresenting different parts of the gastrointestinal tract

As an example of the versatility and potential of humangastrointestinal simulators Table 2 reports a series of studiesabout modulation of gut microbiota by polyphenols usingthe SHIME [57 58]This validatedmodel comprises stomachand small intestinal sections for predigestion of food aswell as vessels stimulating the ascending transcending anddescending parts of the human colon allowing assessment ofchanges in the different colonic areas that are very challengingto access in a human intervention However it should beunderlined that this approach takes for granted that theextracts reach intact the colonic region and no nutrientabsorption is consideredThe use of the SHIME to investigatethe effects of a soy germ powder on the fermentative capacityof the simulated microbiota of the colon was the aim of astudy carried out by De Boever et al [57]They observed thatthe addition of the soy germ powder in a 2-week treatmentresulted into an overall increase of bacterial marker pop-ulations (Enterobacteriaceae coliforms Lactobacillus sppStaphylococcus spp and Clostridium spp) with a significantincrease of 2 log10 units in the Lactobacillus spp populationMore recently Kemperman et al [31] using the twin-SHIME

model studied the influence of a bolus dose and a 2-weekcontinuous administration of complex dietary polyphenolsfrom black tea or red wine grape extracts on the colonicmicrobiota The Twin-SHIME system involving two modelsthat run in parallel was inoculatedwith the same fecal samplefor direct comparison of the effect of the two polyphenoltypes A combination of analyses including cultivation PCR-denaturing gradient gel electrophoresis (DGGE) quantita-tive PCR and high throughput pyrosequencing of the 16Sribosomal RNA gene was applied to characterize micro-bial community changes This study showed that complexpolyphenols in the context of a model system can modulateselect members of the human gut microbiota revealing noveltargets potentially involved in polyphenolmetabolism andorresistant microbes to be further investigated for polyphenolmetabolism or resistance mechanisms [31]

6 Animal Models Studies

It is widely assumed that preliminary evidence should bewarranted in animal models before human interventiontrials Animal models contribute to better understanding themechanisms and biological effects that could be likely tohappen in the human body The metabolism of polyphenolshas been object of numerous animal studies (mostly inrodents) especially for their impact on metabolic disorders[58] but only a few of these studies have followed thedynamics and composition of the intestinal microbiota inassociation with polyphenol metabolites retrieved from thehost Caution is required in extrapolating results to humansbecause culture-independent comparisons have revealed thatmost bacterial genera and species found in mice are not seenin humans although the distal gut microbiota of mice andhumans harbors the same bacterial phyla [59] In this sectionstudies performed in animals in order to assess the effects ofpolyphenols on the modulation of intestinal microbiota are

BioMed Research International 7

Table 3 Animal model studies

Reference Animal Phenoliccompoundfood Dose Treatment

durationMicrobialtechnique Population increase Population decrease

Hara et al(1995) [60] Pigs Tea polyphenols 02 (free access) 2 weeks Plate count Lactobacilli

Total bacteriaBacteroidaceaeC perfringens

Ishihara et al(2001) [61] Calves Green tea extracts 15 gday 4 weeks Plate count

Bifidobacterium sppLactobacillus sppC perfringens

Smith andMackie (2004)[66]

Rats

Proantocyanidinsextracted from

Acaciaangustissima

07 (low tannindiet) and 20

(high tannin diet)

35 weekstreatment +35 weekswashout

PCR-DGGEDot blot

hybridization

Bacteroides fragilisgroup

Bacteroides-Prevotella-

Porphyromonas group

Enterobacteriaceae

C leptum group

Dolara et al(2005) [62] Rats

Red winepolyphenolspowder

50mgkg 16 weeks Plate count LactobacilliBifidobacteria

PropionibacteriaBacteroidesClostridia

Sembries et al(2006) [63] Rats Apple juice free access 4 weeks Plate count Lactobacilli

BifidobacteriaSembries et al(2003) [64] Rats Apple pomace

juice colloid5 suppl diet(free access) 6 weeks Plate count

FISH Bacteroidaceae

Larrosa et al(2009) [68] Rats Resveratrol 1mgkgday 25 days Plate count Lactobacilli

Bifidobacteria

Molan et al(2010) [69] Rats

Blackcurrantextracts (leaf or

berry)

3 timesweek(i) 30mgkg

(leaf)(ii) 134mgkg

(berry)

4 weeks FISH

Lactobacilli (berryextract)

Bifidobacteria (leafand berry extracts)

Viveros et al(2011) [65]

Broilerchicks

Grape pomaceconcentrate(GPC) Grapeseed extract

(GSE)

60 gkg diet(GPC)

72 gkg diet(GSE)

(free access)

21 days Plate countT-RFLP

E coliEnterococcus sppLactobacillus spp

Lacombe et al(2013) [70] Rats Lowbush wild

blueberries

20 g feedday(eq 24 plusmn 52mganthocyaninday)

6 weeks Metagenomicsequencing

Thermonospora sppCorynebacteria spp

Slackia spp

Lactobacillus sppEnterococcus spp

summarized (Table 3) Experiments were mainly performedin rats although other larger animals such as chicks calvesor pigs have also been used Gut microbial communities wereevaluated by diverse methodologies including culture-basedmethods (plate count) DGGE FISH T-RFLP qPCR andmetagenomic sequencing

Animal studies performed in pigs [60] and in calves[61] demonstrated that tea polyphenols administration con-tributed to the improvement in the composition of the intesti-nal microbiota Thus the administration of tea polyphenolsin pigs significantly increased the levels of lactobacilli whilstit diminished the levels of total bacteria and Bacteroidaceaeand a tendency to decrease in lecithinase positive clostridiaincludingC perfringenswas also observed [60] However thereduction rate of Bifidobacterium spp and Lactobacillus sppwas slowwhile that ofC perfringensdecreased faster in calvessupplemented with the green tea extract [61]

Dolara et al [62] showed that treatment with winepolyphenols in carcinogen-treated F344 rats was associated

with a strong variation in the colonic microbiota comparedto the control-fed rats Although the total bacterial counts andanaerobeaerobe ratio of microorganisms in the feces frompolyphenol-treated rats were similar to that from control ratspropionibacteria Bacteroides and Clostridia decreased whilelactobacilli and bifidobacteria increased Based on additionalexperiments these authors concluded that reduction ofoxidative damage modulation of colonic flora and variationin gene expression may be all connected in the action of winepolyphenols on the intestinal function and carcinogenesis

In other study rats fedwith apple juice instead of drinkingwater showed more lactobacilli and bifidobacteria in freshfeces that differed from the controls by one-log10 colonyforming units [63] The same research group studied theeffect of colloids isolated from apple pomace extraction juiceson the intestinal microbiota in Wistar rats An increaseof Bacteroidaceae in almost one-log10 higher counts wasobserved in feces of rats fed with apple juice colloid thancontrol rats [64] Another animal experiment conducted to

8 BioMed Research International

study the effect on intestinal microbiota of the inclusionof grape pomace extracts in the diet of broiler chicks [65]found that for the cecum birds fed grape extracts had higherpopulations of E coli Lactobacillus and Enterococcus speciesthan birds in any other treatment group These authorsconcluded that grape polyphenol-rich products modified thegut morphology and intestinal microbiota and increased thebiodiversity degree of intestinal bacteria in broiler chicks

Inclusion of condensed tannins (proanthocyanidins)extracted from Acacia angustissima on rat diet resulted ina shift in the predominant bacteria towards tannin-resistantGram-negative Enterobacteriaceaeand Bacteroides speciesand reduced the number of Gram-positive C leptum group[66] Compatible results were obtained in an experimentwith rats fed a proanthocyanidin-rich cocoa preparation [67]where the authors found a significant decrease in the propor-tion of Bacteroides Clostridium and Staphylococcus generain the feces of cocoa-fed animals Interestingly reductions inClostridium species were found to correlate with weight lossand decrease in body mass index

Larrosa et al [68] observed an increase in lactobacilliand bifidobacteria when resveratrol (3541015840-trihydroxy-trans-stilbene) which naturally occurs in grapes and grape-derivedfoodstuffs such as red wine was administered to rats Afterinduction of colitis by dextran sulphate sodium proliferationof both E coli and enterobacteria was lower in rats treatedwith resveratrol than in control rats This could be the resultof an indirect effect of resveratrol-supplemented diet whichincreased bifidobacteria and lactobacilli counts preventingthe colonization and invasion of tissues by enterobacteriaincluding E coli

Prebiotic activity of wild blackcurrant extracts observedin in vitro experiments was further confirmed in rats byMolan et al [69] A significant increase in the populationsize of lactobacilli and bifidobacteria was observed after dailyadministration of those extracts to rats Similarly a grapeantioxidant dietary fibre preparation was found to increasethe population of Lactobacillus spp when fed to rats whereaspopulations of Bifidobacterium spp decreased and changes inE coli and Bacteroides vulgatus counts were not significant[50]

Recently Lacombe et al [70] studied the composition andfunctional potential of the colon microbiota from rats feda diet enriched in lowbush wild blueberries Application ofnovel metagenomic techniques (Illumina shotgun sequenc-ing) revealed a significant reduction in the relative abundanceof the genera Lactobacillus and Enterococcus associated withwild blueberries intake In addition hierarchical analysisshowed a significant increase in the relative abundanceof the phylum Actinobacteria the order Actinomycetalesand several novel genera under the family Bifidobacteri-aceae and Coriobacteriaceae in the blueberries group Theauthors indicated that although the microbiome of ratsdiffers from humans the applied model was a powerfultool to study population dynamics and related metabolicfunctions Metagenomic studies can determine microbialcommunity profiles gene presenceabsence and abundanceand functional repertoire however they can only infer an

observed phenotype since a gene presence does not imply itsexpression or functionality [71]

7 Human Intervention Studies

Investigations involving the use of humans potentially pro-vide the best models for studying the interactions of foodcomponents (eg polyphenols) with microbiota although invivo intervention trials hold inevitable practical and ethicallimitations [12] The use of cross-over designs where volun-teers serve as their own control permits multilevel analysisschemes that increase power but requires a relevant numberof volunteers to allow for statistically significant multivariatemodels [72] Up to now only a few studies have examinedthe in vivo impact of dietary polyphenols on the humangut microbiota and most of them were focused on singlepolyphenol molecules and selected bacterial populations Asummary of human intervention studies about effects ofpolyphenols in the modulation of the intestinal microbiotais collected in Table 4 In these studies the polyphenol doseused was much dependent on the type of food preparationand its concentration normally ranging from 01 to 4 thetreatment time was also variable from 10 days to 2 monthsand the applied microbial techniques were diverse (platecount DGGE FISH T-RFLP and qPCR)

In a study with a reduced number of subjects (119899 =8) Okubo et al [73] reported a notably increase in thepercentages of Bifidobacterium spp in total fecal countsafter an intervention with a product containing 70 of teapolyphenols A significant decrease of C perfringens andother Clostridium spp was also observed during the intakeperiod However in a crossover feeding study (number ofvolunteers not reported) that investigated the effects of blacktea drinking on hypercholesterolemic volunteers Mai et al[74] found that although specific bacterial groups were notaffected the total amount of bacteria significantly decreasedhighlighting large interindividual variations More recentlyan intervention study (119899 = 10) by Jin et al [75] confirmedan overall tendency for the proportion of bifidobacteria toincrease because of green tea consumption even thoughthere were interindividual differences in the Bifidobacteriumspecies

Yamakoshi et al [76] showed that administration of aproanthocyanidin-rich extract from grape seeds to healthyvolunteers (119899 = 9) significantly increased the fecal number ofBifidobacterium whereas the number of putrefactive bacteriasuch as enterobacteria tended to decrease The interactionbetween proanthocyanidins and intestinal bacteria was alsoconfirmed in a randomized double-blind crossover andcontrolled intervention study (119899 = 22) ingesting two cocoadrinks exhibiting low and high polyphenol content [77]Compared with the consumption of the low-flavan-3-olcocoa drink the daily consumption of the high-flavan-3-ol cocoa drink significantly increased the bifidobacteria andlactobacilli populations but significantly decreased clostridiacounts

Queipo-Ortuno et al [78] performed a randomizedcrossover and controlled trial (119899 = 10) consisting of theintake of red wine dealcoholized red wine and gin over

BioMed Research International 9

Table4Hum

aninterventio

nstu

dies

Reference

Volunteer

number

Phenolic

compo

undfood

Dose

Treatm

ent

duratio

nMicrobial

techniqu

ePo

pulatio

nincrease

Popu

latio

ndecrease

Noeffect

Oku

boetal

(1994)[73]

8Green

tea

(Sun

phenon

)04g

3tim

esper

day

4weeks

Platec

ount

Cperfr

ingens

Clostridium

spp

Yamakoshi

etal(2001)[76]

9Proantocyanidin-

richextractfrom

grapes

eeds

05g

day

6weeks

Platec

ount

Bifid

obacteriu

mspp

Enterobacteriaceae

Maietal

(200

4)[74]

15Blacktea

700m

gteas

olids5

times

perd

ay21

days

FISH

DGGE

Totalbacteria

Nochanges

Claveletal

(2005)

[83]

39Isofl

avon

es100m

gday

2mon

ths

TTGEFISH

Ccoccoides-E

rectale

grou

pBifid

obacteriu

mspp

Lactobacillus-

Enterococcus

spp

Faecalibacteriu

mprau

snitziisubgroup

Costabileetal

(2008)

[84]

31Who

legrainwheat

cereals

48gday

3weeks

FISH

Bifid

obacteria

Lactob

acilli

Totalbacteria

Bacteroidesspp

C

histo

lyticum

perfringens

grou

pAc

etobacteriu

mspp

Jaqu

etetal

(200

9)[87]

16Coff

ee3cupsday

3weeks

FISH

DGGE

Bifid

obacteriu

mspp

Carvalho

-Wellsetal

(2010)

[85]

32Who

legrainmaize

cereals

48gday

3weeks

FISH

Bifid

obacteria

Totalbacteria

Bacteroidesspp

C

histo

lyticum

perfringens

grou

pAc

etobacteriu

mspp

Gill

etal

(2010)

[80]

10Ra

spberrypu

ree

20gday

4days

PCR-DGGE

Nochangesinthep

rofileo

fcolonicb

acteria

Shinoh

arae

tal(2010)[79]

8Ap

ples

2applesday

2weeks

Platec

ount

Lactobacillus

spp

Streptococcusspp

En

terococcus

spp

Enterobacteriaceae

lecithinase-po

sitive

clostrid

iainclu

ding

Cperfr

ingens

Pseudomonas

spp

10 BioMed Research International

Table4Con

tinued

Reference

Volunteer

number

Phenolic

compo

undfood

Dose

Treatm

ent

duratio

nMicrobial

techniqu

ePo

pulatio

nincrease

Popu

latio

ndecrease

Noeffect

Tzou

nise

tal

(2011)[77]

22Cocoa

flavano

l494m

gday

29mgday

4weeks

FISH

Bifid

obacteriu

mspp

Lactobacillus

spp

Chisto

lyticum

perfringens

grou

p

Vend

ramee

tal(2011)[81]

15Wild

blueberry

drink

25gwild

blueberriesd

ay6weeks

qPCR

Bifid

obacteriu

mspp

Lacidophilus

Bacteroidesspp

Prevotellaspp

Enterococcus

spp

Ccoccoides

Queipo-

Ortun

oetal

(2012)

[78]

10Re

dwine

272m

Lday

20days

qPCR

Enterococcus

spp

Prevotellaspp

Bacteroides

Bifid

obacteriu

mspp

Bacteroidesu

niform

isEggerthella

lenta

Blautia

coccoides-E

rectaleg

roup

Clostridium

spp

Chisto

lyticum

group

Actin

obacteria

Jinetal(2012)

[75]

10Green

tea

1000

mLday

10days

T-RF

LPqP

CRBifid

obacteriu

mspp

Gug

lielm

ettiet

al(2013)[82]

15Wild

blueberries

drink

25gwild

blueberriesd

ay6weeks

qPCR

Blongum

subspinfantis

Cuervo

etal

(2014)

[86]

38

Dairy

prod

ucts

Fruits

Vegetables

Cereals

Food

intake

was

recorded

usingan

annu

alfood

frequ

ency

questio

nnaire

qPCR

Lactobacillus

Bcoccoides

Clep

tum

BioMed Research International 11

three consecutive periods After the red wine period thebacterial concentrations of proteobacteria fusobacteria Fir-micutes and Bacteroidetes markedly increased comparedwith the washout period significant increases in the num-ber of Bifidobacterium spp and Prevotella spp were alsoobserved However Lactobacillus spp Clostridium spp andC histolyticum group concentrations remained unchangedthroughout the study

In a small-scale observational study (119899 = 8) Shinoharaet al [79] found that the number of bifidobacteria in fecessignificantly increased during apple intake and the numbersof Lactobacillus spp Streptococcus spp and Enterococcusspp tended to increase On the contrary enterobacteriaand lecithinase-positive clostridia including C perfringensand Pseudomonas species tended to decrease Howeverthat study did not use culture-independent microbiologytechniques and suffered from the lack of a control groupAlso in relation to fruits another small human interventionstudy (119899 = 10) with raspberry puree [80] did not observestatistically significant alterations in the profile of colonicbacteria probably due to high interindividual variation infecal bacteria although the profiles of microbial metabolitesof raspberry polyphenols varied greatly between individualsindicating that the type of gut microbiota affects cataboliteprofiles released by bacteria in the colonThis lack of effect onthe intestinal microbiota after the intake of raspberry pureemight also be due to the short duration of the treatment aswell as the techniques employed to quantify the intestinalmicrobiota

Vendrame et al [81] studied the potential prebioticactivity of a drink elaborated fromwild blueberries especiallyrich in anthocyanins in a small intervention trial (119899 = 15) Asignificant increase in Bifidobacterium spp and L acidophilusgroup was detected while no significant differences wereobserved for Bacteroides spp Prevotella spp Enterococcusspp and C coccoides In a further paper of the same group[82] seven different intragenus bifidobacteria taxonomicclusters that were among the most common and abundantbifidobacteria species inhabiting the human gutwere targetedin the same samples It was found thatB adolescentisB breveB catenulatumpseudocatenulatum and B longum subsplongumwere always present in the group of subjects enrolledwhereas B bifidum and B longum subsp infantis were notIn spite of the large interindividual variability a significantincrease of B longum subsp infantis cell concentration wasobserved in the feces of volunteers after the wild blueberrydrink treatment which was attributed to the presence ofprebiotic (bifidogenic) molecules from blueberries possiblyfibers and glycosylated anthocyanins

In a study with postmenopausal women (119899 = 39)Clavel et al [83] found that isoflavone supplementationstimulated dominant microorganisms of the C coccoides-Erectale cluster Lactobacillus-Enterococcus group Faecalibac-terium prausnitzii subgroup and Bifidobacterium genus Itwas also suggested that the concentration of C coccoides-Erectale cluster was related to women capacity to excrete equolan intestinal metabolite from daidzein In two interventionstudies with whole grain breakfast cereals from wheat (119899 =31) and maize (119899 = 32) [84 85] the ingestion of both

products resulted in significant increases in fecal bifidobac-teria andor lactobacilli without changing the relative abun-dance of other dominant members of the gut microbiotaLittle or no changes were observed in the numbers of totalbacteria Bacteroides spp C histolyticumperfringens groupand Acetobacterium spp present in the feces However aswhole grains are good sources of dietary fiber it is difficult toascribe the observed effects only to the phenolic compoundspresent in these foods In this respect Cuervo et al [86] haverecently studied the correlations between the intake of fiberand polyphenols from diet and fecal microbiota compositionin a cohort of apparently healthy subjects Results showedthat the intake of soluble pectins and flavanones fromorangespresented a negative correlation with the levels of B coccoidesand C leptum By contrast the intake of white breadproviding hemicellulose and resistant starch was directlycorrelated with Lactobacillus

Finally another human trial (119899 = 16) carried out byJaquet et al [87] assessed the impact of a moderate con-sumption of instant coffee on the general composition ofthe human intestinal bacterial population Coffee bever-ages contain significant amounts of soluble fibre (mainlygalactomannans and arabinogalactan-proteins) and phenoliccompounds (chlorogenic acids) which arewell utilised by thehuman fecal microbiota It was observed that although fecalprofiles of the dominant microbiota were not significantlyaffected after the consumption of the coffee the populationof Bifidobacterium spp increased being the largest increaseobserved for those volunteers showing the lowest initialbifidobacteria levels

8 Conclusions

This review has tried to summarize the current knowledgein relation to the phenolic metabolism by gut microbiota andthemodulation of the gutmicrobiota by phenolic compoundsand polyphenol-rich dietary sourcesThere are evidences thatthe beneficial effects attribute to dietary polyphenols dependon their biotransformation by the gut microbiota Thereforeit is important to investigate the bacterial species impli-cated in the metabolism of dietary polyphenols and furtherresearch is still needed in relation to the resultant microbialmetabolites to ascertain their mechanisms of action Onthe other hand a great number of in vitro and in vivo (inanimals andhumans) studies showing the influence of dietarypolyphenols on gut-inhabiting bacteria have been publishedin recent years Although in vitro assays facilitate experimen-tation caution must be taken in extrapolating results to invivo situation as many factors are acting upon this processIn general in both in vitro and in vivo studies polyphenols orpolyphenol-rich sources have shown to influence the relativeabundance of different bacterial groups within the gut micro-biota reducing numbers of potential pathogens including Cperfringens and C histolyticum and certain Gram-negativeBacteroides spp and enhancing mainly beneficial Clostridiabifidobacteria and lactobacilli A better understanding of theinteraction between dietary polyphenols and gut microbiotathrough the emerging advances in high-throughput meta-genomic transcriptomic and proteomic approaches would

12 BioMed Research International

be essential in order to identify genes and micro-organismsinvolved in polyphenol (in)activation and conversion andthus to elucidate the implications of diet on the modulationof microbiota for delivering health benefits

Functional foods are considered to enhance the protectiveeffects against diseases derived from some food componentsIn the last decades dairy fermented foods have probablybeen one of the most-developed functional products andhave deserved intensive research In this expansion dairyfermented foods have been supplemented with fruits cerealsand other stuffs of plant origin all of which represent a highpercentage of the current market of the dairy industry Theseproducts have a healthy appeal which attracts consumersThus fruit juicesconcentrates and prepared fruits (in theform of pieces pulp and even flour) have been successfullyincorporated in dairy fermented foods as sources of prebioticfibers and phytochemicals Among these phytochemicalspresent in plant-derived foods polyphenols have gainedmuch interest due to their diverse potential beneficial effectsin human health The supplementation of dairy fermentedproducts with rich-polyphenolic stuffs (phenolic extractsphenolic-enriched fractions etc) seems to be an effectivetechnological option to improve the benefits of these productsin the balance of the intestinal microbiota due not only to theaction of the probiotics but also to the potential modulationeffects exerted by polyphenols as it has been described in thisreview Further research in this area will aim to accomplishthe benefits of both probiotic strains and polyphenols inrelation to gut health

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors of this review were funded by the SpanishMINECO through different projects (AGL2012-40172-C02-01 AGL2010-17499 and BFU2012-35228) and the CON-SOLIDER INGENIO 2010 programme (project FUN-C-FOOD CSD2007-063) as well as Comunidad de Madrid(project ALIBIRD P2009AGR-1469) Montserrat Duenaswould like to thank the Spanish ldquoRamon y Cajalrdquo Programmefor a contract

References

[1] S E Power P W OrsquoToole C Stanton R P Ross and GF Fitzgerald ldquoIntestinal microbiota diet and healthrdquo BritishJournal of Nutrition vol 111 no 3 pp 387ndash402 2014

[2] PDeCruz L Prideaux JWagner et al ldquoCharacterization of thegastrointestinal microbiota in health and inflammatory boweldiseaserdquo Inflammatory Bowel Diseases vol 18 no 2 pp 372ndash390 2012

[3] A Kramer S Bekeschus B M Broker H Schleibinger BRazavi and O Assadian ldquoMaintaining health by balancingmicrobial exposure and prevention of infection the hygienehypothesis versus the hypothesis of early immune challengerdquoJournal of Hospital Infection vol 83 no 1 pp S29ndashS34 2013

[4] M Rescigno ldquoIntestinal microbiota and its effects on theimmune systemrdquo Cellular Microbiology vol 16 no 7 pp 1004ndash1013 2014

[5] M G L Hertog E J M Feskens P C H HollmanM B Katanand D Kromhout ldquoDietary antioxidant flavonoids and risk ofcoronary heart disease the Zutphen Elderly StudyrdquoThe Lancetvol 342 no 8878 pp 1007ndash1011 1993

[6] I C W Arts and P C H Hollman ldquoPolyphenols and diseaserisk in epidemiologic studiesrdquoThe American Journal of ClinicalNutrition vol 81 no 1 pp 317Sndash325S 2009

[7] D del Rio A Rodriguez-Mateos J P E Spencer M TognoliniG Borges and A Crozier ldquoDietary (poly)phenolics in humanhealth structures bioavailability and evidence of protectiveeffects against chronic diseasesrdquo Antioxidants amp Redox Signal-ing vol 18 no 14 pp 1818ndash1892 2013

[8] F Perez-Vizcaino and J Duarte ldquoFlavonols and cardiovasculardiseaserdquo Molecular Aspects of Medicine vol 31 no 6 pp 478ndash494 2010

[9] J P E Spencer K Vafeiadou R J Williams and D VauzourldquoNeuroinflammation modulation by flavonoids and mecha-nisms of actionrdquo Molecular Aspects of Medicine vol 33 no 1pp 83ndash97 2012

[10] J M Laparra and Y Sanz ldquoInteractions of gut microbiota withfunctional food components and nutraceuticalsrdquo Pharmacolog-ical Research vol 61 no 3 pp 219ndash225 2010

[11] X He M L Marco and C M Slupsky ldquoEmerging aspects offood and nutrition on gut microbiotardquo Journal of Agriculturaland Food Chemistry vol 61 no 40 pp 9559ndash9574 2013

[12] D Hervert-Hernandez and I Goni ldquoDietary polyphenols andhuman gut microbiota a reviewrdquo Food Reviews Internationalvol 27 no 2 pp 154ndash169 2011

[13] K M Tuohy L Conterno M Gasperotti and R Viola ldquoUp-regulating the human intestinal microbiome using whole plantfoods polyphenols andor fiberrdquo Journal of Agricultural andFood Chemistry vol 60 no 36 pp 8776ndash8782 2012

[14] U Etxeberria A Fernandez-Quintela F I Milagro L AguirreJ A Martınez and M P Portillo ldquoImpact of polyphenols andpolyphenol-rich dietary sources on gut microbiota composi-tionrdquo Journal of Agricultural and Food Chemistry vol 61 no 40pp 9517ndash9533 2013

[15] F Cardona C Andres-Lacueva S Tulipani F J Tinahonesand M I Queipo-Ortuno ldquoBenefits of polyphenols on gutmicrobiota and implications in human healthrdquo Journal ofNutritional Biochemistry vol 24 no 8 pp 1415ndash1422 2013

[16] M V Selma J C Espın and F A Tomas-Barberan ldquoInteractionbetween phenolics and gut microbiota role in human healthrdquoJournal of Agricultural and Food Chemistry vol 57 no 15 pp6485ndash6501 2009

[17] T RequenaMMonagasM A Pozo-Bayon et al ldquoPerspectivesof the potential implications ofwine polyphenols on humanoraland gut microbiotardquo Trends in Food Science amp Technology vol21 no 7 pp 332ndash344 2010

[18] J Van Duynhoven E E Vaughan F van Dorsten et alldquoInteractions of black tea polyphenols with human gut micro-biota implications for gut and cardiovascular health1-4rdquo TheAmerican Journal of Clinical Nutrition vol 98 no 6 pp 1631Sndash1641S 2013

[19] SMoco F-P JMartin and S Rezzi ldquoMetabolomics view on gutmicrobiome modulation by polyphenol-rich foodsrdquo Journal ofProteome Research vol 11 no 10 pp 4781ndash4790 2012

BioMed Research International 13

[20] R K Buddington and P T Sangild ldquoCompanion animalssymposium development of the mammalian gastrointestinaltract the resident microbiota and the role of diet in early liferdquoJournal of Animal Science vol 89 no 5 pp 1506ndash1519 2011

[21] K Tiihonen A C Ouwehand and N Rautonen ldquoHumanintestinal microbiota and healthy ageingrdquo Ageing ResearchReviews vol 9 no 2 pp 107ndash116 2010

[22] D Mariat O Firmesse F Levenez et al ldquoThe firmicutesbacteroidetes ratio of the human microbiota changes with agerdquoBMCMicrobiology vol 9 article 123 2009

[23] M Arumugam J Raes E Pelletier et al ldquoEnterotypes of thehuman gutmicrobiomerdquoNature vol 473 no 7346 pp 174ndash1802011

[24] G D Wu J Chen C Hoffmann et al ldquoLinking long-termdietary patterns with gut microbial enterotypesrdquo Science vol334 no 6052 pp 105ndash108 2011

[25] I B JefferyM J Claesson PWOrsquoToole and F Shanahan ldquoCat-egorization of the gut microbiota enterotypes or gradientsrdquoNature Reviews Microbiology vol 10 no 9 pp 591ndash592 2012

[26] WM de Vos andM Nieuwdorp ldquoGenomics a gut predictionrdquoNature vol 498 no 7452 pp 48ndash49 2013

[27] P B Eckburg E M Bik C N Bernstein et al ldquoMicrobiologydiversity of the human intestinal microbial florardquo Science vol308 no 5728 pp 1635ndash1638 2005

[28] E G Zoetendal C T Collier S Koike R I Mackie and H RGaskins ldquoMolecular ecological analysis of the gastrointestinalmicrobiota a reviewrdquo Journal of Nutrition vol 134 no 2 pp465ndash472 2004

[29] M H Fraher PW OrsquoToole and E MM Quigley ldquoTechniquesused to characterize the gut microbiota a guide for the clini-cianrdquo Nature Reviews Gastroenterology and Hepatology vol 9no 6 pp 312ndash322 2012

[30] R A Kemperman S Bolca L C Roger and E E VaughanldquoNovel approaches for analysing gut microbes and dietarypolyphenols challenges and opportunitiesrdquo Microbiology vol156 no 11 pp 3224ndash3231 2010

[31] R A Kemperman G Gross S Mondot et al ldquoImpact ofpolyphenols from black tea and red winegrape juice on a gutmodel microbiomerdquo Food Research International vol 53 no 2pp 659ndash669 2013

[32] M N Clifford ldquoDiet-derived phenols in plasma and tissues andtheir implications for healthrdquo Planta Medica vol 70 no 12 pp1103ndash1114 2004

[33] A Crozier D del Rio and M N Clifford ldquoBioavailability ofdietary flavonoids and phenolic compoundsrdquoMolecular Aspectsof Medicine vol 31 no 6 pp 446ndash467 2010

[34] A J Day M S Dupont S Ridley et al ldquoDeglycosylation offlavonoid and isoflavonoid glycosides by human small intestineand liver beta-glucosidase activityrdquo FEBS Letters vol 436 no 1pp 71ndash75 1998

[35] A J Day F J Canada J C Dıaz et al ldquoDietary flavonoid andisoflavone glycosides are hydrolysed by the lactase site of lactasephlorizin hydrolaserdquo FEBS Letters vol 468 no 2-3 pp 166ndash1702000

[36] A Scalbert and G Williamson ldquoDietary intake and bioavail-ability of polyphenolsrdquo Journal of Nutrition vol 130 no 8 pp2073Sndash2085S 2000

[37] A R Rechner G Kuhnle H Hu et al ldquoThe metabolism ofdietary polyphenols and the relevance to circulating levels ofconjugated metabolitesrdquo Free Radical Research vol 36 no 11pp 1229ndash1241 2002

[38] A-M Aura K A OrsquoLeary G Williamson et al ldquoQuercetinderivatives are deconjugated and converted to hydroxypheny-lacetic acids but not methylated by human fecal flora in vitrordquoJournal of Agricultural and Food Chemistry vol 50 no 6 pp1725ndash1730 2002

[39] A-M Aura ldquoMicrobial metabolism of dietary phenolic com-pounds in the colonrdquo Phytochemistry Reviews vol 7 no 3 pp407ndash429 2008

[40] M Monagas M Urpi-Sarda F Sanchez-Patan et al ldquoInsightsinto themetabolism andmicrobial biotransformation of dietaryflavan-3-ols and the bioactivity of their metabolitesrdquo Food andFunction vol 1 no 3 pp 233ndash253 2010

[41] GWilliamson andMNClifford ldquoColonicmetabolites of berrypolyphenols the missing link to biological activityrdquo BritishJournal of Nutrition vol 104 no 3 pp S48ndashS66 2010

[42] D M Jacobs E Gaudier J van Duynhoven and E E VaughanldquoNon-digestible food ingredients colonic microbiota and theimpact on gut health and immunity a role for metabolomicsrdquoCurrent Drug Metabolism vol 10 no 1 pp 41ndash54 2009

[43] S Bolca S Possemiers V Maervoet et al ldquoMicrobial anddietary factors associatedwith the 8-prenylnaringenin producerphenotype a dietary intervention trial with fifty healthy post-menopausal Caucasian womenrdquo British Journal of Nutritionvol 98 no 5 pp 950ndash959 2007

[44] X Tzounis J Vulevic G G C Kuhnle et al ldquoFlavanolmonomer-induced changes to the human faecal microflorardquoBritish Journal of Nutrition vol 99 no 4 pp 782ndash792 2008

[45] M Hidalgo M J Oruna-Concha S Kolida et al ldquoMetabolismof anthocyanins by human gut microflora and their influenceon gut bacterial growthrdquo Journal of Agricultural and FoodChemistry vol 60 no 15 pp 3882ndash3890 2012

[46] A L Molan M A Lila J Mawson and S De ldquoIn vitroand in vivo evaluation of the prebiotic activity of water-soluble blueberry extractsrdquo World Journal of Microbiology andBiotechnology vol 25 no 7 pp 1243ndash1249 2009

[47] D Bialonska P Ramnani S G Kasimsetty K R Muntha GR Gibson and D Ferreira ldquoThe influence of pomegranate by-product and punicalagins on selected groups of human intesti-nal microbiotardquo International Journal of FoodMicrobiology vol140 no 2-3 pp 175ndash182 2010

[48] G Mandalari R M Faulks C Bisignano K W Waldron ANarbad and M S J Wickham ldquoIn vitro evaluation of theprebiotic properties of almond skins (Amygdalus communisL)rdquoFEMS Microbiology Letters vol 304 no 2 pp 116ndash122 2010

[49] V Fogliano M L Corollaro P Vitaglione et al ldquoIn vitro bioac-cessibility and gut biotransformation of polyphenols present inthe water-insoluble cocoa fractionrdquoMolecular Nutritionamp FoodResearch vol 55 supplement 1 pp S44ndashS55 2011

[50] M J Pozuelo A Agis-Torres D Hervert-Hernandez etal ldquoGrape antioxidant dietary fiber stimulates Lactobacillusgrowth in rat cecumrdquo Journal of Food Science vol 77 no 2 ppH59ndashH62 2012

[51] C Cueva F Sanchez-Patan M Monagas et al ldquoIn vitrofermentation of grape seed flavan-3-ol fractions by humanfaecal microbiota changes in microbial groups and phenolicmetabolitesrdquo FEMSMicrobiology Ecology vol 83 no 3 pp 792ndash805 2013

[52] F Sanchez-Patan C CuevaMMonagas et al ldquoIn vitro fermen-tation of a red wine extract by human gut microbiota changesin microbial groups and formation of phenolic metabolitesrdquoJournal of Agricultural and Food Chemistry vol 60 no 9 pp2136ndash2147 2012

14 BioMed Research International

[53] E Barroso F Sanchez-Patan P J Martın-Alvarez et al ldquoLacto-bacillus plantarum IFPL935 favors the initial metabolism of redwine polyphenols when added to a colonic microbiotardquo Journalof Agricultural and Food Chemistry vol 61 no 42 pp 10163ndash10172 2013

[54] G R Gibson J H Cummings and G T Macfarlane ldquoUse ofa three-stage continuous culture system to study the effect ofmucin on dissimilatory sulfate reduction and methanogenesisby mixed populations of human gut bacteriardquo Applied andEnvironmentalMicrobiology vol 54 no 11 pp 2750ndash2755 1988

[55] KMollyMVandeWoestyne andWVerstraete ldquoDevelopmentof a 5-step multi-chamber reactor as a simulation of thehuman intestinal microbial ecosystemrdquo Applied Microbiologyand Biotechnology vol 39 no 2 pp 254ndash258 1993

[56] M Minekus M Smeets-Peeters A Bernalier et al ldquoAcomputer-controlled system to simulate conditions of thelarge intestine with peristaltic mixing water absorption andabsorption of fermentation productsrdquoAppliedMicrobiology andBiotechnology vol 53 no 1 pp 108ndash114 1999

[57] PDeBoever BDeplancke andWVerstraete ldquoFermentation bygut microbiota cultured in a simulator of the human intestinalmicrobial ecosystem is improved by supplementing a soygermpowderrdquo Journal of Nutrition vol 130 no 10 pp 2599ndash26062000

[58] C S Yang X Wang G Lu and S C Picinich ldquoCancerprevention by tea animal studies molecular mechanisms andhuman relevancerdquoNature Reviews Cancer vol 9 no 6 pp 429ndash439 2009

[59] R E Ley F Backhed P Turnbaugh C A Lozupone R DKnight and J I Gordon ldquoObesity alters gut microbial ecologyrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 102 no 31 pp 11070ndash11075 2005

[60] H Hara N Orita S Hatano et al ldquoEffect of tea polyphenols onfecal flora and fecal metabolic products of pigsrdquo The Journal ofVeterinary Medical Science vol 57 no 1 pp 45ndash49 1995

[61] N Ishihara D-C Chu S Akachi and L R Juneja ldquoImprove-ment of intestinal microflora balance and prevention of diges-tive and respiratory organ diseases in calves by green teaextractsrdquo Livestock Production Science vol 68 no 2-3 pp 217ndash229 2001

[62] P Dolara C Luceri C De Filippo et al ldquoRed wine polyphenolsinfluence carcinogenesis intestinal microflora oxidative dam-age and gene expression profiles of colonicmucosa in F344 ratsrdquoMutation Research-Fundamental and Molecular Mechanisms ofMutagenesis vol 591 no 1-2 pp 237ndash246 2005

[63] S Sembries G Dongowski K Mehrlander F Will and HDietrich ldquoPhysiological effects of extraction juices from applegrape and red beet pomaces in ratsrdquo Journal of Agricultural andFood Chemistry vol 54 no 26 pp 10269ndash10280 2006

[64] S Sembries G Dongowski G Jacobasch K Mehrlander FWill andH Dietrich ldquoEffects of dietary fibre-rich juice colloidsfrom apple pomace extraction juices on intestinal fermentationproducts and microbiota in ratsrdquo British Journal of Nutritionvol 90 no 3 pp 607ndash615 2003

[65] A Viveros S Chamorro M Pizarro I Arija C Centeno andA Brenes ldquoEffects of dietary polyphenol-rich grape productson intestinal microflora and gut morphology in broiler chicksrdquoPoultry Science vol 90 no 3 pp 566ndash578 2011

[66] A H Smith and R I Mackie ldquoEffect of condensed tannins onbacterial diversity andmetabolic activity in the rat gastrointesti-nal tractrdquo Applied and Environmental Microbiology vol 70 no2 pp 1104ndash1115 2004

[67] M Massot-Cladera T Perez-Berezo A Franch M Castelland F J Perez-Cano ldquoCocoa modulatory effect on rat faecalmicrobiota and colonic crosstalkrdquo Archives of Biochemistry andBiophysics vol 527 no 2 pp 105ndash112 2012

[68] M Larrosa M J Yanez-Gascon M V Selma et al ldquoEffectof a low dose of dietary resveratrol on colon microbiotainflammation and tissue damage in a DSS-induced colitis ratmodelrdquo Journal of Agricultural and Food Chemistry vol 57 no6 pp 2211ndash2220 2009

[69] A-L Molan Z Liu andM Kruger ldquoThe ability of blackcurrantextracts to positively modulate key markers of gastrointestinalfunction in ratsrdquoWorld Journal ofMicrobiologyampBiotechnologyvol 26 no 10 pp 1735ndash1743 2010

[70] A Lacombe R W Li D Klimis-Zacas et al ldquoLowbush wildblueberries have the potential to modify gut microbiota andxenobiotic metabolism in the rat colonrdquo PLoS ONE vol 8 no6 Article ID e67497 2013

[71] R Saad M R Rizkallah and R K Aziz ldquoGut Pharmacomicro-biomics the tip of an iceberg of complex interactions betweendrugs and gut-associated microbesrdquo Gut Pathogens vol 4 no1 article 16 2012

[72] E J J Van Velzen J A Westerhuis J P M van Duynhovenet al ldquoMultilevel data analysis of a crossover designed humannutritional intervention studyrdquo Journal of Proteome Researchvol 7 no 10 pp 4483ndash4491 2008

[73] T Okubo N Ishihara H Takahashi et al ldquoEffects of partiallyhydrolyzed guar gum intake on human intestinal microfloraand itsmetabolismrdquoBioscience Biotechnology andBiochemistryvol 58 no 8 pp 1364ndash1369 1994

[74] V Mai H A Katki H Harmsen et al ldquoEffects of a controlleddiet and black tea drinking on the fecalmicroflora compositionand the fecal bile acid profile of human volunteers in a double-blinded ramdomized feeding studyrdquo The Journal of Nutritionvol 134 no 2 pp 473ndash478 2004

[75] J-S Jin M Touyama T Hisada and Y Benno ldquoEffectsof green tea consumption on human fecal microbiota withspecial reference to Bifidobacterium speciesrdquoMicrobiology andImmunology vol 56 no 11 pp 729ndash739 2012

[76] J Yamakoshi S Tokutake M Kikuchi Y Kubota H Konishiand T Mitsuoka ldquoEffect of proantocyanidin -rich extract fromgrape seed on human fecal flora and fecalodorrdquo FASEB Journalvol 15 no 4 p A633 2001

[77] X Tzounis A Rodriguez-Mateos J Vulevic G R Gibson CKwik-Uribe and J P E Spencer ldquoPrebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomizedcontrolled double-blind crossover intervention studyrdquo TheAmerican Journal of Clinical Nutrition vol 93 no 1 pp 62ndash722011

[78] M I Queipo-Ortuno M Boto-Ordonez M Murri et alldquoInfluence of red wine polyphenols and ethanol on the gutmicrobiota ecology and biochemical biomarkersrdquo AmericanJournal of Clinical Nutrition vol 95 no 6 pp 1323ndash1334 2012

[79] K Shinohara Y Ohashi K Kawasumi A Terada and TFujisawa ldquoEffect of apple intake on fecal microbiota andmetabolites in humansrdquo Anaerobe vol 16 no 5 pp 510ndash5152010

[80] C I R Gill G J Mcdougall S Glidewell et al ldquoProfiling ofphenols in human fecal water after raspberry supplementationrdquoJournal of Agricultural and Food Chemistry vol 58 no 19 pp10389ndash10395 2010

[81] S Vendrame S Guglielmetti P Riso S Arioli D Klimis-Zacasand M Porrini ldquoSix-week consumption of a wild blueberry

BioMed Research International 15

powder drink increases Bifidobacteria in the human gutrdquoJournal of Agricultural and Food Chemistry vol 59 no 24 pp12815ndash12820 2011

[82] S Guglielmetti D Fracassetti V Taverniti et al ldquoDifferentialmodulation of human intestinal Bifidobacterium populationsafter consumption of a wild blueberry (Vaccinium angusti-folium) drinkrdquo Journal of Agricultural and Food Chemistry vol61 no 34 pp 8134ndash8140 2013

[83] T Clavel M Fallani P Lepage et al ldquoIsoflavones and func-tional foods alter the dominant intestinal microbiota in post-menopausal womenrdquo Journal of Nutrition vol 135 no 12 pp2786ndash2792 2005

[84] A Costabile A Klinder F Fava et al ldquoWhole-grain wheatbreakfast cereal has a prebiotic effect on the human gut micro-biota a double-blind placebo-controlled crossover studyrdquoBritish Journal of Nutrition vol 99 no 1 pp 110ndash120 2008

[85] A L Carvalho-Wells K Helmolz C Nodet et al ldquoDetermina-tion of the in vivo prebiotic potential of a maize-based wholegrain breakfast cereal a human feeding studyrdquo British Journalof Nutrition vol 104 no 9 pp 1353ndash1356 2010

[86] A Cuervo L Valdes N Salazar et al ldquoPilot study of diet andmicrobiota interactive associations of fibers and polyphenolswith human intestinal bacteriardquo Journal of Agricultural andFood Chemistry vol 62 no 23 pp 5330ndash5336 2014

[87] M Jaquet I Rochat J Moulin C Cavin and R BibilonildquoImpact of coffee consumption on the gut microbiota a humanvolunteer studyrdquo International Journal of FoodMicrobiology vol130 no 2 pp 117ndash121 2009

Submit your manuscripts athttpwwwhindawicom

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Page 7: Review Article A Survey of Modulation of Gut Microbiota by ...downloads.hindawi.com/journals/bmri/2015/850902.pdf · Review Article A Survey of Modulation of Gut Microbiota by Dietary

BioMed Research International 7

Table 3 Animal model studies

Reference Animal Phenoliccompoundfood Dose Treatment

durationMicrobialtechnique Population increase Population decrease

Hara et al(1995) [60] Pigs Tea polyphenols 02 (free access) 2 weeks Plate count Lactobacilli

Total bacteriaBacteroidaceaeC perfringens

Ishihara et al(2001) [61] Calves Green tea extracts 15 gday 4 weeks Plate count

Bifidobacterium sppLactobacillus sppC perfringens

Smith andMackie (2004)[66]

Rats

Proantocyanidinsextracted from

Acaciaangustissima

07 (low tannindiet) and 20

(high tannin diet)

35 weekstreatment +35 weekswashout

PCR-DGGEDot blot

hybridization

Bacteroides fragilisgroup

Bacteroides-Prevotella-

Porphyromonas group

Enterobacteriaceae

C leptum group

Dolara et al(2005) [62] Rats

Red winepolyphenolspowder

50mgkg 16 weeks Plate count LactobacilliBifidobacteria

PropionibacteriaBacteroidesClostridia

Sembries et al(2006) [63] Rats Apple juice free access 4 weeks Plate count Lactobacilli

BifidobacteriaSembries et al(2003) [64] Rats Apple pomace

juice colloid5 suppl diet(free access) 6 weeks Plate count

FISH Bacteroidaceae

Larrosa et al(2009) [68] Rats Resveratrol 1mgkgday 25 days Plate count Lactobacilli

Bifidobacteria

Molan et al(2010) [69] Rats

Blackcurrantextracts (leaf or

berry)

3 timesweek(i) 30mgkg

(leaf)(ii) 134mgkg

(berry)

4 weeks FISH

Lactobacilli (berryextract)

Bifidobacteria (leafand berry extracts)

Viveros et al(2011) [65]

Broilerchicks

Grape pomaceconcentrate(GPC) Grapeseed extract

(GSE)

60 gkg diet(GPC)

72 gkg diet(GSE)

(free access)

21 days Plate countT-RFLP

E coliEnterococcus sppLactobacillus spp

Lacombe et al(2013) [70] Rats Lowbush wild

blueberries

20 g feedday(eq 24 plusmn 52mganthocyaninday)

6 weeks Metagenomicsequencing

Thermonospora sppCorynebacteria spp

Slackia spp

Lactobacillus sppEnterococcus spp

summarized (Table 3) Experiments were mainly performedin rats although other larger animals such as chicks calvesor pigs have also been used Gut microbial communities wereevaluated by diverse methodologies including culture-basedmethods (plate count) DGGE FISH T-RFLP qPCR andmetagenomic sequencing

Animal studies performed in pigs [60] and in calves[61] demonstrated that tea polyphenols administration con-tributed to the improvement in the composition of the intesti-nal microbiota Thus the administration of tea polyphenolsin pigs significantly increased the levels of lactobacilli whilstit diminished the levels of total bacteria and Bacteroidaceaeand a tendency to decrease in lecithinase positive clostridiaincludingC perfringenswas also observed [60] However thereduction rate of Bifidobacterium spp and Lactobacillus sppwas slowwhile that ofC perfringensdecreased faster in calvessupplemented with the green tea extract [61]

Dolara et al [62] showed that treatment with winepolyphenols in carcinogen-treated F344 rats was associated

with a strong variation in the colonic microbiota comparedto the control-fed rats Although the total bacterial counts andanaerobeaerobe ratio of microorganisms in the feces frompolyphenol-treated rats were similar to that from control ratspropionibacteria Bacteroides and Clostridia decreased whilelactobacilli and bifidobacteria increased Based on additionalexperiments these authors concluded that reduction ofoxidative damage modulation of colonic flora and variationin gene expression may be all connected in the action of winepolyphenols on the intestinal function and carcinogenesis

In other study rats fedwith apple juice instead of drinkingwater showed more lactobacilli and bifidobacteria in freshfeces that differed from the controls by one-log10 colonyforming units [63] The same research group studied theeffect of colloids isolated from apple pomace extraction juiceson the intestinal microbiota in Wistar rats An increaseof Bacteroidaceae in almost one-log10 higher counts wasobserved in feces of rats fed with apple juice colloid thancontrol rats [64] Another animal experiment conducted to

8 BioMed Research International

study the effect on intestinal microbiota of the inclusionof grape pomace extracts in the diet of broiler chicks [65]found that for the cecum birds fed grape extracts had higherpopulations of E coli Lactobacillus and Enterococcus speciesthan birds in any other treatment group These authorsconcluded that grape polyphenol-rich products modified thegut morphology and intestinal microbiota and increased thebiodiversity degree of intestinal bacteria in broiler chicks

Inclusion of condensed tannins (proanthocyanidins)extracted from Acacia angustissima on rat diet resulted ina shift in the predominant bacteria towards tannin-resistantGram-negative Enterobacteriaceaeand Bacteroides speciesand reduced the number of Gram-positive C leptum group[66] Compatible results were obtained in an experimentwith rats fed a proanthocyanidin-rich cocoa preparation [67]where the authors found a significant decrease in the propor-tion of Bacteroides Clostridium and Staphylococcus generain the feces of cocoa-fed animals Interestingly reductions inClostridium species were found to correlate with weight lossand decrease in body mass index

Larrosa et al [68] observed an increase in lactobacilliand bifidobacteria when resveratrol (3541015840-trihydroxy-trans-stilbene) which naturally occurs in grapes and grape-derivedfoodstuffs such as red wine was administered to rats Afterinduction of colitis by dextran sulphate sodium proliferationof both E coli and enterobacteria was lower in rats treatedwith resveratrol than in control rats This could be the resultof an indirect effect of resveratrol-supplemented diet whichincreased bifidobacteria and lactobacilli counts preventingthe colonization and invasion of tissues by enterobacteriaincluding E coli

Prebiotic activity of wild blackcurrant extracts observedin in vitro experiments was further confirmed in rats byMolan et al [69] A significant increase in the populationsize of lactobacilli and bifidobacteria was observed after dailyadministration of those extracts to rats Similarly a grapeantioxidant dietary fibre preparation was found to increasethe population of Lactobacillus spp when fed to rats whereaspopulations of Bifidobacterium spp decreased and changes inE coli and Bacteroides vulgatus counts were not significant[50]

Recently Lacombe et al [70] studied the composition andfunctional potential of the colon microbiota from rats feda diet enriched in lowbush wild blueberries Application ofnovel metagenomic techniques (Illumina shotgun sequenc-ing) revealed a significant reduction in the relative abundanceof the genera Lactobacillus and Enterococcus associated withwild blueberries intake In addition hierarchical analysisshowed a significant increase in the relative abundanceof the phylum Actinobacteria the order Actinomycetalesand several novel genera under the family Bifidobacteri-aceae and Coriobacteriaceae in the blueberries group Theauthors indicated that although the microbiome of ratsdiffers from humans the applied model was a powerfultool to study population dynamics and related metabolicfunctions Metagenomic studies can determine microbialcommunity profiles gene presenceabsence and abundanceand functional repertoire however they can only infer an

observed phenotype since a gene presence does not imply itsexpression or functionality [71]

7 Human Intervention Studies

Investigations involving the use of humans potentially pro-vide the best models for studying the interactions of foodcomponents (eg polyphenols) with microbiota although invivo intervention trials hold inevitable practical and ethicallimitations [12] The use of cross-over designs where volun-teers serve as their own control permits multilevel analysisschemes that increase power but requires a relevant numberof volunteers to allow for statistically significant multivariatemodels [72] Up to now only a few studies have examinedthe in vivo impact of dietary polyphenols on the humangut microbiota and most of them were focused on singlepolyphenol molecules and selected bacterial populations Asummary of human intervention studies about effects ofpolyphenols in the modulation of the intestinal microbiotais collected in Table 4 In these studies the polyphenol doseused was much dependent on the type of food preparationand its concentration normally ranging from 01 to 4 thetreatment time was also variable from 10 days to 2 monthsand the applied microbial techniques were diverse (platecount DGGE FISH T-RFLP and qPCR)

In a study with a reduced number of subjects (119899 =8) Okubo et al [73] reported a notably increase in thepercentages of Bifidobacterium spp in total fecal countsafter an intervention with a product containing 70 of teapolyphenols A significant decrease of C perfringens andother Clostridium spp was also observed during the intakeperiod However in a crossover feeding study (number ofvolunteers not reported) that investigated the effects of blacktea drinking on hypercholesterolemic volunteers Mai et al[74] found that although specific bacterial groups were notaffected the total amount of bacteria significantly decreasedhighlighting large interindividual variations More recentlyan intervention study (119899 = 10) by Jin et al [75] confirmedan overall tendency for the proportion of bifidobacteria toincrease because of green tea consumption even thoughthere were interindividual differences in the Bifidobacteriumspecies

Yamakoshi et al [76] showed that administration of aproanthocyanidin-rich extract from grape seeds to healthyvolunteers (119899 = 9) significantly increased the fecal number ofBifidobacterium whereas the number of putrefactive bacteriasuch as enterobacteria tended to decrease The interactionbetween proanthocyanidins and intestinal bacteria was alsoconfirmed in a randomized double-blind crossover andcontrolled intervention study (119899 = 22) ingesting two cocoadrinks exhibiting low and high polyphenol content [77]Compared with the consumption of the low-flavan-3-olcocoa drink the daily consumption of the high-flavan-3-ol cocoa drink significantly increased the bifidobacteria andlactobacilli populations but significantly decreased clostridiacounts

Queipo-Ortuno et al [78] performed a randomizedcrossover and controlled trial (119899 = 10) consisting of theintake of red wine dealcoholized red wine and gin over

BioMed Research International 9

Table4Hum

aninterventio

nstu

dies

Reference

Volunteer

number

Phenolic

compo

undfood

Dose

Treatm

ent

duratio

nMicrobial

techniqu

ePo

pulatio

nincrease

Popu

latio

ndecrease

Noeffect

Oku

boetal

(1994)[73]

8Green

tea

(Sun

phenon

)04g

3tim

esper

day

4weeks

Platec

ount

Cperfr

ingens

Clostridium

spp

Yamakoshi

etal(2001)[76]

9Proantocyanidin-

richextractfrom

grapes

eeds

05g

day

6weeks

Platec

ount

Bifid

obacteriu

mspp

Enterobacteriaceae

Maietal

(200

4)[74]

15Blacktea

700m

gteas

olids5

times

perd

ay21

days

FISH

DGGE

Totalbacteria

Nochanges

Claveletal

(2005)

[83]

39Isofl

avon

es100m

gday

2mon

ths

TTGEFISH

Ccoccoides-E

rectale

grou

pBifid

obacteriu

mspp

Lactobacillus-

Enterococcus

spp

Faecalibacteriu

mprau

snitziisubgroup

Costabileetal

(2008)

[84]

31Who

legrainwheat

cereals

48gday

3weeks

FISH

Bifid

obacteria

Lactob

acilli

Totalbacteria

Bacteroidesspp

C

histo

lyticum

perfringens

grou

pAc

etobacteriu

mspp

Jaqu

etetal

(200

9)[87]

16Coff

ee3cupsday

3weeks

FISH

DGGE

Bifid

obacteriu

mspp

Carvalho

-Wellsetal

(2010)

[85]

32Who

legrainmaize

cereals

48gday

3weeks

FISH

Bifid

obacteria

Totalbacteria

Bacteroidesspp

C

histo

lyticum

perfringens

grou

pAc

etobacteriu

mspp

Gill

etal

(2010)

[80]

10Ra

spberrypu

ree

20gday

4days

PCR-DGGE

Nochangesinthep

rofileo

fcolonicb

acteria

Shinoh

arae

tal(2010)[79]

8Ap

ples

2applesday

2weeks

Platec

ount

Lactobacillus

spp

Streptococcusspp

En

terococcus

spp

Enterobacteriaceae

lecithinase-po

sitive

clostrid

iainclu

ding

Cperfr

ingens

Pseudomonas

spp

10 BioMed Research International

Table4Con

tinued

Reference

Volunteer

number

Phenolic

compo

undfood

Dose

Treatm

ent

duratio

nMicrobial

techniqu

ePo

pulatio

nincrease

Popu

latio

ndecrease

Noeffect

Tzou

nise

tal

(2011)[77]

22Cocoa

flavano

l494m

gday

29mgday

4weeks

FISH

Bifid

obacteriu

mspp

Lactobacillus

spp

Chisto

lyticum

perfringens

grou

p

Vend

ramee

tal(2011)[81]

15Wild

blueberry

drink

25gwild

blueberriesd

ay6weeks

qPCR

Bifid

obacteriu

mspp

Lacidophilus

Bacteroidesspp

Prevotellaspp

Enterococcus

spp

Ccoccoides

Queipo-

Ortun

oetal

(2012)

[78]

10Re

dwine

272m

Lday

20days

qPCR

Enterococcus

spp

Prevotellaspp

Bacteroides

Bifid

obacteriu

mspp

Bacteroidesu

niform

isEggerthella

lenta

Blautia

coccoides-E

rectaleg

roup

Clostridium

spp

Chisto

lyticum

group

Actin

obacteria

Jinetal(2012)

[75]

10Green

tea

1000

mLday

10days

T-RF

LPqP

CRBifid

obacteriu

mspp

Gug

lielm

ettiet

al(2013)[82]

15Wild

blueberries

drink

25gwild

blueberriesd

ay6weeks

qPCR

Blongum

subspinfantis

Cuervo

etal

(2014)

[86]

38

Dairy

prod

ucts

Fruits

Vegetables

Cereals

Food

intake

was

recorded

usingan

annu

alfood

frequ

ency

questio

nnaire

qPCR

Lactobacillus

Bcoccoides

Clep

tum

BioMed Research International 11

three consecutive periods After the red wine period thebacterial concentrations of proteobacteria fusobacteria Fir-micutes and Bacteroidetes markedly increased comparedwith the washout period significant increases in the num-ber of Bifidobacterium spp and Prevotella spp were alsoobserved However Lactobacillus spp Clostridium spp andC histolyticum group concentrations remained unchangedthroughout the study

In a small-scale observational study (119899 = 8) Shinoharaet al [79] found that the number of bifidobacteria in fecessignificantly increased during apple intake and the numbersof Lactobacillus spp Streptococcus spp and Enterococcusspp tended to increase On the contrary enterobacteriaand lecithinase-positive clostridia including C perfringensand Pseudomonas species tended to decrease Howeverthat study did not use culture-independent microbiologytechniques and suffered from the lack of a control groupAlso in relation to fruits another small human interventionstudy (119899 = 10) with raspberry puree [80] did not observestatistically significant alterations in the profile of colonicbacteria probably due to high interindividual variation infecal bacteria although the profiles of microbial metabolitesof raspberry polyphenols varied greatly between individualsindicating that the type of gut microbiota affects cataboliteprofiles released by bacteria in the colonThis lack of effect onthe intestinal microbiota after the intake of raspberry pureemight also be due to the short duration of the treatment aswell as the techniques employed to quantify the intestinalmicrobiota

Vendrame et al [81] studied the potential prebioticactivity of a drink elaborated fromwild blueberries especiallyrich in anthocyanins in a small intervention trial (119899 = 15) Asignificant increase in Bifidobacterium spp and L acidophilusgroup was detected while no significant differences wereobserved for Bacteroides spp Prevotella spp Enterococcusspp and C coccoides In a further paper of the same group[82] seven different intragenus bifidobacteria taxonomicclusters that were among the most common and abundantbifidobacteria species inhabiting the human gutwere targetedin the same samples It was found thatB adolescentisB breveB catenulatumpseudocatenulatum and B longum subsplongumwere always present in the group of subjects enrolledwhereas B bifidum and B longum subsp infantis were notIn spite of the large interindividual variability a significantincrease of B longum subsp infantis cell concentration wasobserved in the feces of volunteers after the wild blueberrydrink treatment which was attributed to the presence ofprebiotic (bifidogenic) molecules from blueberries possiblyfibers and glycosylated anthocyanins

In a study with postmenopausal women (119899 = 39)Clavel et al [83] found that isoflavone supplementationstimulated dominant microorganisms of the C coccoides-Erectale cluster Lactobacillus-Enterococcus group Faecalibac-terium prausnitzii subgroup and Bifidobacterium genus Itwas also suggested that the concentration of C coccoides-Erectale cluster was related to women capacity to excrete equolan intestinal metabolite from daidzein In two interventionstudies with whole grain breakfast cereals from wheat (119899 =31) and maize (119899 = 32) [84 85] the ingestion of both

products resulted in significant increases in fecal bifidobac-teria andor lactobacilli without changing the relative abun-dance of other dominant members of the gut microbiotaLittle or no changes were observed in the numbers of totalbacteria Bacteroides spp C histolyticumperfringens groupand Acetobacterium spp present in the feces However aswhole grains are good sources of dietary fiber it is difficult toascribe the observed effects only to the phenolic compoundspresent in these foods In this respect Cuervo et al [86] haverecently studied the correlations between the intake of fiberand polyphenols from diet and fecal microbiota compositionin a cohort of apparently healthy subjects Results showedthat the intake of soluble pectins and flavanones fromorangespresented a negative correlation with the levels of B coccoidesand C leptum By contrast the intake of white breadproviding hemicellulose and resistant starch was directlycorrelated with Lactobacillus

Finally another human trial (119899 = 16) carried out byJaquet et al [87] assessed the impact of a moderate con-sumption of instant coffee on the general composition ofthe human intestinal bacterial population Coffee bever-ages contain significant amounts of soluble fibre (mainlygalactomannans and arabinogalactan-proteins) and phenoliccompounds (chlorogenic acids) which arewell utilised by thehuman fecal microbiota It was observed that although fecalprofiles of the dominant microbiota were not significantlyaffected after the consumption of the coffee the populationof Bifidobacterium spp increased being the largest increaseobserved for those volunteers showing the lowest initialbifidobacteria levels

8 Conclusions

This review has tried to summarize the current knowledgein relation to the phenolic metabolism by gut microbiota andthemodulation of the gutmicrobiota by phenolic compoundsand polyphenol-rich dietary sourcesThere are evidences thatthe beneficial effects attribute to dietary polyphenols dependon their biotransformation by the gut microbiota Thereforeit is important to investigate the bacterial species impli-cated in the metabolism of dietary polyphenols and furtherresearch is still needed in relation to the resultant microbialmetabolites to ascertain their mechanisms of action Onthe other hand a great number of in vitro and in vivo (inanimals andhumans) studies showing the influence of dietarypolyphenols on gut-inhabiting bacteria have been publishedin recent years Although in vitro assays facilitate experimen-tation caution must be taken in extrapolating results to invivo situation as many factors are acting upon this processIn general in both in vitro and in vivo studies polyphenols orpolyphenol-rich sources have shown to influence the relativeabundance of different bacterial groups within the gut micro-biota reducing numbers of potential pathogens including Cperfringens and C histolyticum and certain Gram-negativeBacteroides spp and enhancing mainly beneficial Clostridiabifidobacteria and lactobacilli A better understanding of theinteraction between dietary polyphenols and gut microbiotathrough the emerging advances in high-throughput meta-genomic transcriptomic and proteomic approaches would

12 BioMed Research International

be essential in order to identify genes and micro-organismsinvolved in polyphenol (in)activation and conversion andthus to elucidate the implications of diet on the modulationof microbiota for delivering health benefits

Functional foods are considered to enhance the protectiveeffects against diseases derived from some food componentsIn the last decades dairy fermented foods have probablybeen one of the most-developed functional products andhave deserved intensive research In this expansion dairyfermented foods have been supplemented with fruits cerealsand other stuffs of plant origin all of which represent a highpercentage of the current market of the dairy industry Theseproducts have a healthy appeal which attracts consumersThus fruit juicesconcentrates and prepared fruits (in theform of pieces pulp and even flour) have been successfullyincorporated in dairy fermented foods as sources of prebioticfibers and phytochemicals Among these phytochemicalspresent in plant-derived foods polyphenols have gainedmuch interest due to their diverse potential beneficial effectsin human health The supplementation of dairy fermentedproducts with rich-polyphenolic stuffs (phenolic extractsphenolic-enriched fractions etc) seems to be an effectivetechnological option to improve the benefits of these productsin the balance of the intestinal microbiota due not only to theaction of the probiotics but also to the potential modulationeffects exerted by polyphenols as it has been described in thisreview Further research in this area will aim to accomplishthe benefits of both probiotic strains and polyphenols inrelation to gut health

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors of this review were funded by the SpanishMINECO through different projects (AGL2012-40172-C02-01 AGL2010-17499 and BFU2012-35228) and the CON-SOLIDER INGENIO 2010 programme (project FUN-C-FOOD CSD2007-063) as well as Comunidad de Madrid(project ALIBIRD P2009AGR-1469) Montserrat Duenaswould like to thank the Spanish ldquoRamon y Cajalrdquo Programmefor a contract

References

[1] S E Power P W OrsquoToole C Stanton R P Ross and GF Fitzgerald ldquoIntestinal microbiota diet and healthrdquo BritishJournal of Nutrition vol 111 no 3 pp 387ndash402 2014

[2] PDeCruz L Prideaux JWagner et al ldquoCharacterization of thegastrointestinal microbiota in health and inflammatory boweldiseaserdquo Inflammatory Bowel Diseases vol 18 no 2 pp 372ndash390 2012

[3] A Kramer S Bekeschus B M Broker H Schleibinger BRazavi and O Assadian ldquoMaintaining health by balancingmicrobial exposure and prevention of infection the hygienehypothesis versus the hypothesis of early immune challengerdquoJournal of Hospital Infection vol 83 no 1 pp S29ndashS34 2013

[4] M Rescigno ldquoIntestinal microbiota and its effects on theimmune systemrdquo Cellular Microbiology vol 16 no 7 pp 1004ndash1013 2014

[5] M G L Hertog E J M Feskens P C H HollmanM B Katanand D Kromhout ldquoDietary antioxidant flavonoids and risk ofcoronary heart disease the Zutphen Elderly StudyrdquoThe Lancetvol 342 no 8878 pp 1007ndash1011 1993

[6] I C W Arts and P C H Hollman ldquoPolyphenols and diseaserisk in epidemiologic studiesrdquoThe American Journal of ClinicalNutrition vol 81 no 1 pp 317Sndash325S 2009

[7] D del Rio A Rodriguez-Mateos J P E Spencer M TognoliniG Borges and A Crozier ldquoDietary (poly)phenolics in humanhealth structures bioavailability and evidence of protectiveeffects against chronic diseasesrdquo Antioxidants amp Redox Signal-ing vol 18 no 14 pp 1818ndash1892 2013

[8] F Perez-Vizcaino and J Duarte ldquoFlavonols and cardiovasculardiseaserdquo Molecular Aspects of Medicine vol 31 no 6 pp 478ndash494 2010

[9] J P E Spencer K Vafeiadou R J Williams and D VauzourldquoNeuroinflammation modulation by flavonoids and mecha-nisms of actionrdquo Molecular Aspects of Medicine vol 33 no 1pp 83ndash97 2012

[10] J M Laparra and Y Sanz ldquoInteractions of gut microbiota withfunctional food components and nutraceuticalsrdquo Pharmacolog-ical Research vol 61 no 3 pp 219ndash225 2010

[11] X He M L Marco and C M Slupsky ldquoEmerging aspects offood and nutrition on gut microbiotardquo Journal of Agriculturaland Food Chemistry vol 61 no 40 pp 9559ndash9574 2013

[12] D Hervert-Hernandez and I Goni ldquoDietary polyphenols andhuman gut microbiota a reviewrdquo Food Reviews Internationalvol 27 no 2 pp 154ndash169 2011

[13] K M Tuohy L Conterno M Gasperotti and R Viola ldquoUp-regulating the human intestinal microbiome using whole plantfoods polyphenols andor fiberrdquo Journal of Agricultural andFood Chemistry vol 60 no 36 pp 8776ndash8782 2012

[14] U Etxeberria A Fernandez-Quintela F I Milagro L AguirreJ A Martınez and M P Portillo ldquoImpact of polyphenols andpolyphenol-rich dietary sources on gut microbiota composi-tionrdquo Journal of Agricultural and Food Chemistry vol 61 no 40pp 9517ndash9533 2013

[15] F Cardona C Andres-Lacueva S Tulipani F J Tinahonesand M I Queipo-Ortuno ldquoBenefits of polyphenols on gutmicrobiota and implications in human healthrdquo Journal ofNutritional Biochemistry vol 24 no 8 pp 1415ndash1422 2013

[16] M V Selma J C Espın and F A Tomas-Barberan ldquoInteractionbetween phenolics and gut microbiota role in human healthrdquoJournal of Agricultural and Food Chemistry vol 57 no 15 pp6485ndash6501 2009

[17] T RequenaMMonagasM A Pozo-Bayon et al ldquoPerspectivesof the potential implications ofwine polyphenols on humanoraland gut microbiotardquo Trends in Food Science amp Technology vol21 no 7 pp 332ndash344 2010

[18] J Van Duynhoven E E Vaughan F van Dorsten et alldquoInteractions of black tea polyphenols with human gut micro-biota implications for gut and cardiovascular health1-4rdquo TheAmerican Journal of Clinical Nutrition vol 98 no 6 pp 1631Sndash1641S 2013

[19] SMoco F-P JMartin and S Rezzi ldquoMetabolomics view on gutmicrobiome modulation by polyphenol-rich foodsrdquo Journal ofProteome Research vol 11 no 10 pp 4781ndash4790 2012

BioMed Research International 13

[20] R K Buddington and P T Sangild ldquoCompanion animalssymposium development of the mammalian gastrointestinaltract the resident microbiota and the role of diet in early liferdquoJournal of Animal Science vol 89 no 5 pp 1506ndash1519 2011

[21] K Tiihonen A C Ouwehand and N Rautonen ldquoHumanintestinal microbiota and healthy ageingrdquo Ageing ResearchReviews vol 9 no 2 pp 107ndash116 2010

[22] D Mariat O Firmesse F Levenez et al ldquoThe firmicutesbacteroidetes ratio of the human microbiota changes with agerdquoBMCMicrobiology vol 9 article 123 2009

[23] M Arumugam J Raes E Pelletier et al ldquoEnterotypes of thehuman gutmicrobiomerdquoNature vol 473 no 7346 pp 174ndash1802011

[24] G D Wu J Chen C Hoffmann et al ldquoLinking long-termdietary patterns with gut microbial enterotypesrdquo Science vol334 no 6052 pp 105ndash108 2011

[25] I B JefferyM J Claesson PWOrsquoToole and F Shanahan ldquoCat-egorization of the gut microbiota enterotypes or gradientsrdquoNature Reviews Microbiology vol 10 no 9 pp 591ndash592 2012

[26] WM de Vos andM Nieuwdorp ldquoGenomics a gut predictionrdquoNature vol 498 no 7452 pp 48ndash49 2013

[27] P B Eckburg E M Bik C N Bernstein et al ldquoMicrobiologydiversity of the human intestinal microbial florardquo Science vol308 no 5728 pp 1635ndash1638 2005

[28] E G Zoetendal C T Collier S Koike R I Mackie and H RGaskins ldquoMolecular ecological analysis of the gastrointestinalmicrobiota a reviewrdquo Journal of Nutrition vol 134 no 2 pp465ndash472 2004

[29] M H Fraher PW OrsquoToole and E MM Quigley ldquoTechniquesused to characterize the gut microbiota a guide for the clini-cianrdquo Nature Reviews Gastroenterology and Hepatology vol 9no 6 pp 312ndash322 2012

[30] R A Kemperman S Bolca L C Roger and E E VaughanldquoNovel approaches for analysing gut microbes and dietarypolyphenols challenges and opportunitiesrdquo Microbiology vol156 no 11 pp 3224ndash3231 2010

[31] R A Kemperman G Gross S Mondot et al ldquoImpact ofpolyphenols from black tea and red winegrape juice on a gutmodel microbiomerdquo Food Research International vol 53 no 2pp 659ndash669 2013

[32] M N Clifford ldquoDiet-derived phenols in plasma and tissues andtheir implications for healthrdquo Planta Medica vol 70 no 12 pp1103ndash1114 2004

[33] A Crozier D del Rio and M N Clifford ldquoBioavailability ofdietary flavonoids and phenolic compoundsrdquoMolecular Aspectsof Medicine vol 31 no 6 pp 446ndash467 2010

[34] A J Day M S Dupont S Ridley et al ldquoDeglycosylation offlavonoid and isoflavonoid glycosides by human small intestineand liver beta-glucosidase activityrdquo FEBS Letters vol 436 no 1pp 71ndash75 1998

[35] A J Day F J Canada J C Dıaz et al ldquoDietary flavonoid andisoflavone glycosides are hydrolysed by the lactase site of lactasephlorizin hydrolaserdquo FEBS Letters vol 468 no 2-3 pp 166ndash1702000

[36] A Scalbert and G Williamson ldquoDietary intake and bioavail-ability of polyphenolsrdquo Journal of Nutrition vol 130 no 8 pp2073Sndash2085S 2000

[37] A R Rechner G Kuhnle H Hu et al ldquoThe metabolism ofdietary polyphenols and the relevance to circulating levels ofconjugated metabolitesrdquo Free Radical Research vol 36 no 11pp 1229ndash1241 2002

[38] A-M Aura K A OrsquoLeary G Williamson et al ldquoQuercetinderivatives are deconjugated and converted to hydroxypheny-lacetic acids but not methylated by human fecal flora in vitrordquoJournal of Agricultural and Food Chemistry vol 50 no 6 pp1725ndash1730 2002

[39] A-M Aura ldquoMicrobial metabolism of dietary phenolic com-pounds in the colonrdquo Phytochemistry Reviews vol 7 no 3 pp407ndash429 2008

[40] M Monagas M Urpi-Sarda F Sanchez-Patan et al ldquoInsightsinto themetabolism andmicrobial biotransformation of dietaryflavan-3-ols and the bioactivity of their metabolitesrdquo Food andFunction vol 1 no 3 pp 233ndash253 2010

[41] GWilliamson andMNClifford ldquoColonicmetabolites of berrypolyphenols the missing link to biological activityrdquo BritishJournal of Nutrition vol 104 no 3 pp S48ndashS66 2010

[42] D M Jacobs E Gaudier J van Duynhoven and E E VaughanldquoNon-digestible food ingredients colonic microbiota and theimpact on gut health and immunity a role for metabolomicsrdquoCurrent Drug Metabolism vol 10 no 1 pp 41ndash54 2009

[43] S Bolca S Possemiers V Maervoet et al ldquoMicrobial anddietary factors associatedwith the 8-prenylnaringenin producerphenotype a dietary intervention trial with fifty healthy post-menopausal Caucasian womenrdquo British Journal of Nutritionvol 98 no 5 pp 950ndash959 2007

[44] X Tzounis J Vulevic G G C Kuhnle et al ldquoFlavanolmonomer-induced changes to the human faecal microflorardquoBritish Journal of Nutrition vol 99 no 4 pp 782ndash792 2008

[45] M Hidalgo M J Oruna-Concha S Kolida et al ldquoMetabolismof anthocyanins by human gut microflora and their influenceon gut bacterial growthrdquo Journal of Agricultural and FoodChemistry vol 60 no 15 pp 3882ndash3890 2012

[46] A L Molan M A Lila J Mawson and S De ldquoIn vitroand in vivo evaluation of the prebiotic activity of water-soluble blueberry extractsrdquo World Journal of Microbiology andBiotechnology vol 25 no 7 pp 1243ndash1249 2009

[47] D Bialonska P Ramnani S G Kasimsetty K R Muntha GR Gibson and D Ferreira ldquoThe influence of pomegranate by-product and punicalagins on selected groups of human intesti-nal microbiotardquo International Journal of FoodMicrobiology vol140 no 2-3 pp 175ndash182 2010

[48] G Mandalari R M Faulks C Bisignano K W Waldron ANarbad and M S J Wickham ldquoIn vitro evaluation of theprebiotic properties of almond skins (Amygdalus communisL)rdquoFEMS Microbiology Letters vol 304 no 2 pp 116ndash122 2010

[49] V Fogliano M L Corollaro P Vitaglione et al ldquoIn vitro bioac-cessibility and gut biotransformation of polyphenols present inthe water-insoluble cocoa fractionrdquoMolecular Nutritionamp FoodResearch vol 55 supplement 1 pp S44ndashS55 2011

[50] M J Pozuelo A Agis-Torres D Hervert-Hernandez etal ldquoGrape antioxidant dietary fiber stimulates Lactobacillusgrowth in rat cecumrdquo Journal of Food Science vol 77 no 2 ppH59ndashH62 2012

[51] C Cueva F Sanchez-Patan M Monagas et al ldquoIn vitrofermentation of grape seed flavan-3-ol fractions by humanfaecal microbiota changes in microbial groups and phenolicmetabolitesrdquo FEMSMicrobiology Ecology vol 83 no 3 pp 792ndash805 2013

[52] F Sanchez-Patan C CuevaMMonagas et al ldquoIn vitro fermen-tation of a red wine extract by human gut microbiota changesin microbial groups and formation of phenolic metabolitesrdquoJournal of Agricultural and Food Chemistry vol 60 no 9 pp2136ndash2147 2012

14 BioMed Research International

[53] E Barroso F Sanchez-Patan P J Martın-Alvarez et al ldquoLacto-bacillus plantarum IFPL935 favors the initial metabolism of redwine polyphenols when added to a colonic microbiotardquo Journalof Agricultural and Food Chemistry vol 61 no 42 pp 10163ndash10172 2013

[54] G R Gibson J H Cummings and G T Macfarlane ldquoUse ofa three-stage continuous culture system to study the effect ofmucin on dissimilatory sulfate reduction and methanogenesisby mixed populations of human gut bacteriardquo Applied andEnvironmentalMicrobiology vol 54 no 11 pp 2750ndash2755 1988

[55] KMollyMVandeWoestyne andWVerstraete ldquoDevelopmentof a 5-step multi-chamber reactor as a simulation of thehuman intestinal microbial ecosystemrdquo Applied Microbiologyand Biotechnology vol 39 no 2 pp 254ndash258 1993

[56] M Minekus M Smeets-Peeters A Bernalier et al ldquoAcomputer-controlled system to simulate conditions of thelarge intestine with peristaltic mixing water absorption andabsorption of fermentation productsrdquoAppliedMicrobiology andBiotechnology vol 53 no 1 pp 108ndash114 1999

[57] PDeBoever BDeplancke andWVerstraete ldquoFermentation bygut microbiota cultured in a simulator of the human intestinalmicrobial ecosystem is improved by supplementing a soygermpowderrdquo Journal of Nutrition vol 130 no 10 pp 2599ndash26062000

[58] C S Yang X Wang G Lu and S C Picinich ldquoCancerprevention by tea animal studies molecular mechanisms andhuman relevancerdquoNature Reviews Cancer vol 9 no 6 pp 429ndash439 2009

[59] R E Ley F Backhed P Turnbaugh C A Lozupone R DKnight and J I Gordon ldquoObesity alters gut microbial ecologyrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 102 no 31 pp 11070ndash11075 2005

[60] H Hara N Orita S Hatano et al ldquoEffect of tea polyphenols onfecal flora and fecal metabolic products of pigsrdquo The Journal ofVeterinary Medical Science vol 57 no 1 pp 45ndash49 1995

[61] N Ishihara D-C Chu S Akachi and L R Juneja ldquoImprove-ment of intestinal microflora balance and prevention of diges-tive and respiratory organ diseases in calves by green teaextractsrdquo Livestock Production Science vol 68 no 2-3 pp 217ndash229 2001

[62] P Dolara C Luceri C De Filippo et al ldquoRed wine polyphenolsinfluence carcinogenesis intestinal microflora oxidative dam-age and gene expression profiles of colonicmucosa in F344 ratsrdquoMutation Research-Fundamental and Molecular Mechanisms ofMutagenesis vol 591 no 1-2 pp 237ndash246 2005

[63] S Sembries G Dongowski K Mehrlander F Will and HDietrich ldquoPhysiological effects of extraction juices from applegrape and red beet pomaces in ratsrdquo Journal of Agricultural andFood Chemistry vol 54 no 26 pp 10269ndash10280 2006

[64] S Sembries G Dongowski G Jacobasch K Mehrlander FWill andH Dietrich ldquoEffects of dietary fibre-rich juice colloidsfrom apple pomace extraction juices on intestinal fermentationproducts and microbiota in ratsrdquo British Journal of Nutritionvol 90 no 3 pp 607ndash615 2003

[65] A Viveros S Chamorro M Pizarro I Arija C Centeno andA Brenes ldquoEffects of dietary polyphenol-rich grape productson intestinal microflora and gut morphology in broiler chicksrdquoPoultry Science vol 90 no 3 pp 566ndash578 2011

[66] A H Smith and R I Mackie ldquoEffect of condensed tannins onbacterial diversity andmetabolic activity in the rat gastrointesti-nal tractrdquo Applied and Environmental Microbiology vol 70 no2 pp 1104ndash1115 2004

[67] M Massot-Cladera T Perez-Berezo A Franch M Castelland F J Perez-Cano ldquoCocoa modulatory effect on rat faecalmicrobiota and colonic crosstalkrdquo Archives of Biochemistry andBiophysics vol 527 no 2 pp 105ndash112 2012

[68] M Larrosa M J Yanez-Gascon M V Selma et al ldquoEffectof a low dose of dietary resveratrol on colon microbiotainflammation and tissue damage in a DSS-induced colitis ratmodelrdquo Journal of Agricultural and Food Chemistry vol 57 no6 pp 2211ndash2220 2009

[69] A-L Molan Z Liu andM Kruger ldquoThe ability of blackcurrantextracts to positively modulate key markers of gastrointestinalfunction in ratsrdquoWorld Journal ofMicrobiologyampBiotechnologyvol 26 no 10 pp 1735ndash1743 2010

[70] A Lacombe R W Li D Klimis-Zacas et al ldquoLowbush wildblueberries have the potential to modify gut microbiota andxenobiotic metabolism in the rat colonrdquo PLoS ONE vol 8 no6 Article ID e67497 2013

[71] R Saad M R Rizkallah and R K Aziz ldquoGut Pharmacomicro-biomics the tip of an iceberg of complex interactions betweendrugs and gut-associated microbesrdquo Gut Pathogens vol 4 no1 article 16 2012

[72] E J J Van Velzen J A Westerhuis J P M van Duynhovenet al ldquoMultilevel data analysis of a crossover designed humannutritional intervention studyrdquo Journal of Proteome Researchvol 7 no 10 pp 4483ndash4491 2008

[73] T Okubo N Ishihara H Takahashi et al ldquoEffects of partiallyhydrolyzed guar gum intake on human intestinal microfloraand itsmetabolismrdquoBioscience Biotechnology andBiochemistryvol 58 no 8 pp 1364ndash1369 1994

[74] V Mai H A Katki H Harmsen et al ldquoEffects of a controlleddiet and black tea drinking on the fecalmicroflora compositionand the fecal bile acid profile of human volunteers in a double-blinded ramdomized feeding studyrdquo The Journal of Nutritionvol 134 no 2 pp 473ndash478 2004

[75] J-S Jin M Touyama T Hisada and Y Benno ldquoEffectsof green tea consumption on human fecal microbiota withspecial reference to Bifidobacterium speciesrdquoMicrobiology andImmunology vol 56 no 11 pp 729ndash739 2012

[76] J Yamakoshi S Tokutake M Kikuchi Y Kubota H Konishiand T Mitsuoka ldquoEffect of proantocyanidin -rich extract fromgrape seed on human fecal flora and fecalodorrdquo FASEB Journalvol 15 no 4 p A633 2001

[77] X Tzounis A Rodriguez-Mateos J Vulevic G R Gibson CKwik-Uribe and J P E Spencer ldquoPrebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomizedcontrolled double-blind crossover intervention studyrdquo TheAmerican Journal of Clinical Nutrition vol 93 no 1 pp 62ndash722011

[78] M I Queipo-Ortuno M Boto-Ordonez M Murri et alldquoInfluence of red wine polyphenols and ethanol on the gutmicrobiota ecology and biochemical biomarkersrdquo AmericanJournal of Clinical Nutrition vol 95 no 6 pp 1323ndash1334 2012

[79] K Shinohara Y Ohashi K Kawasumi A Terada and TFujisawa ldquoEffect of apple intake on fecal microbiota andmetabolites in humansrdquo Anaerobe vol 16 no 5 pp 510ndash5152010

[80] C I R Gill G J Mcdougall S Glidewell et al ldquoProfiling ofphenols in human fecal water after raspberry supplementationrdquoJournal of Agricultural and Food Chemistry vol 58 no 19 pp10389ndash10395 2010

[81] S Vendrame S Guglielmetti P Riso S Arioli D Klimis-Zacasand M Porrini ldquoSix-week consumption of a wild blueberry

BioMed Research International 15

powder drink increases Bifidobacteria in the human gutrdquoJournal of Agricultural and Food Chemistry vol 59 no 24 pp12815ndash12820 2011

[82] S Guglielmetti D Fracassetti V Taverniti et al ldquoDifferentialmodulation of human intestinal Bifidobacterium populationsafter consumption of a wild blueberry (Vaccinium angusti-folium) drinkrdquo Journal of Agricultural and Food Chemistry vol61 no 34 pp 8134ndash8140 2013

[83] T Clavel M Fallani P Lepage et al ldquoIsoflavones and func-tional foods alter the dominant intestinal microbiota in post-menopausal womenrdquo Journal of Nutrition vol 135 no 12 pp2786ndash2792 2005

[84] A Costabile A Klinder F Fava et al ldquoWhole-grain wheatbreakfast cereal has a prebiotic effect on the human gut micro-biota a double-blind placebo-controlled crossover studyrdquoBritish Journal of Nutrition vol 99 no 1 pp 110ndash120 2008

[85] A L Carvalho-Wells K Helmolz C Nodet et al ldquoDetermina-tion of the in vivo prebiotic potential of a maize-based wholegrain breakfast cereal a human feeding studyrdquo British Journalof Nutrition vol 104 no 9 pp 1353ndash1356 2010

[86] A Cuervo L Valdes N Salazar et al ldquoPilot study of diet andmicrobiota interactive associations of fibers and polyphenolswith human intestinal bacteriardquo Journal of Agricultural andFood Chemistry vol 62 no 23 pp 5330ndash5336 2014

[87] M Jaquet I Rochat J Moulin C Cavin and R BibilonildquoImpact of coffee consumption on the gut microbiota a humanvolunteer studyrdquo International Journal of FoodMicrobiology vol130 no 2 pp 117ndash121 2009

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Page 8: Review Article A Survey of Modulation of Gut Microbiota by ...downloads.hindawi.com/journals/bmri/2015/850902.pdf · Review Article A Survey of Modulation of Gut Microbiota by Dietary

8 BioMed Research International

study the effect on intestinal microbiota of the inclusionof grape pomace extracts in the diet of broiler chicks [65]found that for the cecum birds fed grape extracts had higherpopulations of E coli Lactobacillus and Enterococcus speciesthan birds in any other treatment group These authorsconcluded that grape polyphenol-rich products modified thegut morphology and intestinal microbiota and increased thebiodiversity degree of intestinal bacteria in broiler chicks

Inclusion of condensed tannins (proanthocyanidins)extracted from Acacia angustissima on rat diet resulted ina shift in the predominant bacteria towards tannin-resistantGram-negative Enterobacteriaceaeand Bacteroides speciesand reduced the number of Gram-positive C leptum group[66] Compatible results were obtained in an experimentwith rats fed a proanthocyanidin-rich cocoa preparation [67]where the authors found a significant decrease in the propor-tion of Bacteroides Clostridium and Staphylococcus generain the feces of cocoa-fed animals Interestingly reductions inClostridium species were found to correlate with weight lossand decrease in body mass index

Larrosa et al [68] observed an increase in lactobacilliand bifidobacteria when resveratrol (3541015840-trihydroxy-trans-stilbene) which naturally occurs in grapes and grape-derivedfoodstuffs such as red wine was administered to rats Afterinduction of colitis by dextran sulphate sodium proliferationof both E coli and enterobacteria was lower in rats treatedwith resveratrol than in control rats This could be the resultof an indirect effect of resveratrol-supplemented diet whichincreased bifidobacteria and lactobacilli counts preventingthe colonization and invasion of tissues by enterobacteriaincluding E coli

Prebiotic activity of wild blackcurrant extracts observedin in vitro experiments was further confirmed in rats byMolan et al [69] A significant increase in the populationsize of lactobacilli and bifidobacteria was observed after dailyadministration of those extracts to rats Similarly a grapeantioxidant dietary fibre preparation was found to increasethe population of Lactobacillus spp when fed to rats whereaspopulations of Bifidobacterium spp decreased and changes inE coli and Bacteroides vulgatus counts were not significant[50]

Recently Lacombe et al [70] studied the composition andfunctional potential of the colon microbiota from rats feda diet enriched in lowbush wild blueberries Application ofnovel metagenomic techniques (Illumina shotgun sequenc-ing) revealed a significant reduction in the relative abundanceof the genera Lactobacillus and Enterococcus associated withwild blueberries intake In addition hierarchical analysisshowed a significant increase in the relative abundanceof the phylum Actinobacteria the order Actinomycetalesand several novel genera under the family Bifidobacteri-aceae and Coriobacteriaceae in the blueberries group Theauthors indicated that although the microbiome of ratsdiffers from humans the applied model was a powerfultool to study population dynamics and related metabolicfunctions Metagenomic studies can determine microbialcommunity profiles gene presenceabsence and abundanceand functional repertoire however they can only infer an

observed phenotype since a gene presence does not imply itsexpression or functionality [71]

7 Human Intervention Studies

Investigations involving the use of humans potentially pro-vide the best models for studying the interactions of foodcomponents (eg polyphenols) with microbiota although invivo intervention trials hold inevitable practical and ethicallimitations [12] The use of cross-over designs where volun-teers serve as their own control permits multilevel analysisschemes that increase power but requires a relevant numberof volunteers to allow for statistically significant multivariatemodels [72] Up to now only a few studies have examinedthe in vivo impact of dietary polyphenols on the humangut microbiota and most of them were focused on singlepolyphenol molecules and selected bacterial populations Asummary of human intervention studies about effects ofpolyphenols in the modulation of the intestinal microbiotais collected in Table 4 In these studies the polyphenol doseused was much dependent on the type of food preparationand its concentration normally ranging from 01 to 4 thetreatment time was also variable from 10 days to 2 monthsand the applied microbial techniques were diverse (platecount DGGE FISH T-RFLP and qPCR)

In a study with a reduced number of subjects (119899 =8) Okubo et al [73] reported a notably increase in thepercentages of Bifidobacterium spp in total fecal countsafter an intervention with a product containing 70 of teapolyphenols A significant decrease of C perfringens andother Clostridium spp was also observed during the intakeperiod However in a crossover feeding study (number ofvolunteers not reported) that investigated the effects of blacktea drinking on hypercholesterolemic volunteers Mai et al[74] found that although specific bacterial groups were notaffected the total amount of bacteria significantly decreasedhighlighting large interindividual variations More recentlyan intervention study (119899 = 10) by Jin et al [75] confirmedan overall tendency for the proportion of bifidobacteria toincrease because of green tea consumption even thoughthere were interindividual differences in the Bifidobacteriumspecies

Yamakoshi et al [76] showed that administration of aproanthocyanidin-rich extract from grape seeds to healthyvolunteers (119899 = 9) significantly increased the fecal number ofBifidobacterium whereas the number of putrefactive bacteriasuch as enterobacteria tended to decrease The interactionbetween proanthocyanidins and intestinal bacteria was alsoconfirmed in a randomized double-blind crossover andcontrolled intervention study (119899 = 22) ingesting two cocoadrinks exhibiting low and high polyphenol content [77]Compared with the consumption of the low-flavan-3-olcocoa drink the daily consumption of the high-flavan-3-ol cocoa drink significantly increased the bifidobacteria andlactobacilli populations but significantly decreased clostridiacounts

Queipo-Ortuno et al [78] performed a randomizedcrossover and controlled trial (119899 = 10) consisting of theintake of red wine dealcoholized red wine and gin over

BioMed Research International 9

Table4Hum

aninterventio

nstu

dies

Reference

Volunteer

number

Phenolic

compo

undfood

Dose

Treatm

ent

duratio

nMicrobial

techniqu

ePo

pulatio

nincrease

Popu

latio

ndecrease

Noeffect

Oku

boetal

(1994)[73]

8Green

tea

(Sun

phenon

)04g

3tim

esper

day

4weeks

Platec

ount

Cperfr

ingens

Clostridium

spp

Yamakoshi

etal(2001)[76]

9Proantocyanidin-

richextractfrom

grapes

eeds

05g

day

6weeks

Platec

ount

Bifid

obacteriu

mspp

Enterobacteriaceae

Maietal

(200

4)[74]

15Blacktea

700m

gteas

olids5

times

perd

ay21

days

FISH

DGGE

Totalbacteria

Nochanges

Claveletal

(2005)

[83]

39Isofl

avon

es100m

gday

2mon

ths

TTGEFISH

Ccoccoides-E

rectale

grou

pBifid

obacteriu

mspp

Lactobacillus-

Enterococcus

spp

Faecalibacteriu

mprau

snitziisubgroup

Costabileetal

(2008)

[84]

31Who

legrainwheat

cereals

48gday

3weeks

FISH

Bifid

obacteria

Lactob

acilli

Totalbacteria

Bacteroidesspp

C

histo

lyticum

perfringens

grou

pAc

etobacteriu

mspp

Jaqu

etetal

(200

9)[87]

16Coff

ee3cupsday

3weeks

FISH

DGGE

Bifid

obacteriu

mspp

Carvalho

-Wellsetal

(2010)

[85]

32Who

legrainmaize

cereals

48gday

3weeks

FISH

Bifid

obacteria

Totalbacteria

Bacteroidesspp

C

histo

lyticum

perfringens

grou

pAc

etobacteriu

mspp

Gill

etal

(2010)

[80]

10Ra

spberrypu

ree

20gday

4days

PCR-DGGE

Nochangesinthep

rofileo

fcolonicb

acteria

Shinoh

arae

tal(2010)[79]

8Ap

ples

2applesday

2weeks

Platec

ount

Lactobacillus

spp

Streptococcusspp

En

terococcus

spp

Enterobacteriaceae

lecithinase-po

sitive

clostrid

iainclu

ding

Cperfr

ingens

Pseudomonas

spp

10 BioMed Research International

Table4Con

tinued

Reference

Volunteer

number

Phenolic

compo

undfood

Dose

Treatm

ent

duratio

nMicrobial

techniqu

ePo

pulatio

nincrease

Popu

latio

ndecrease

Noeffect

Tzou

nise

tal

(2011)[77]

22Cocoa

flavano

l494m

gday

29mgday

4weeks

FISH

Bifid

obacteriu

mspp

Lactobacillus

spp

Chisto

lyticum

perfringens

grou

p

Vend

ramee

tal(2011)[81]

15Wild

blueberry

drink

25gwild

blueberriesd

ay6weeks

qPCR

Bifid

obacteriu

mspp

Lacidophilus

Bacteroidesspp

Prevotellaspp

Enterococcus

spp

Ccoccoides

Queipo-

Ortun

oetal

(2012)

[78]

10Re

dwine

272m

Lday

20days

qPCR

Enterococcus

spp

Prevotellaspp

Bacteroides

Bifid

obacteriu

mspp

Bacteroidesu

niform

isEggerthella

lenta

Blautia

coccoides-E

rectaleg

roup

Clostridium

spp

Chisto

lyticum

group

Actin

obacteria

Jinetal(2012)

[75]

10Green

tea

1000

mLday

10days

T-RF

LPqP

CRBifid

obacteriu

mspp

Gug

lielm

ettiet

al(2013)[82]

15Wild

blueberries

drink

25gwild

blueberriesd

ay6weeks

qPCR

Blongum

subspinfantis

Cuervo

etal

(2014)

[86]

38

Dairy

prod

ucts

Fruits

Vegetables

Cereals

Food

intake

was

recorded

usingan

annu

alfood

frequ

ency

questio

nnaire

qPCR

Lactobacillus

Bcoccoides

Clep

tum

BioMed Research International 11

three consecutive periods After the red wine period thebacterial concentrations of proteobacteria fusobacteria Fir-micutes and Bacteroidetes markedly increased comparedwith the washout period significant increases in the num-ber of Bifidobacterium spp and Prevotella spp were alsoobserved However Lactobacillus spp Clostridium spp andC histolyticum group concentrations remained unchangedthroughout the study

In a small-scale observational study (119899 = 8) Shinoharaet al [79] found that the number of bifidobacteria in fecessignificantly increased during apple intake and the numbersof Lactobacillus spp Streptococcus spp and Enterococcusspp tended to increase On the contrary enterobacteriaand lecithinase-positive clostridia including C perfringensand Pseudomonas species tended to decrease Howeverthat study did not use culture-independent microbiologytechniques and suffered from the lack of a control groupAlso in relation to fruits another small human interventionstudy (119899 = 10) with raspberry puree [80] did not observestatistically significant alterations in the profile of colonicbacteria probably due to high interindividual variation infecal bacteria although the profiles of microbial metabolitesof raspberry polyphenols varied greatly between individualsindicating that the type of gut microbiota affects cataboliteprofiles released by bacteria in the colonThis lack of effect onthe intestinal microbiota after the intake of raspberry pureemight also be due to the short duration of the treatment aswell as the techniques employed to quantify the intestinalmicrobiota

Vendrame et al [81] studied the potential prebioticactivity of a drink elaborated fromwild blueberries especiallyrich in anthocyanins in a small intervention trial (119899 = 15) Asignificant increase in Bifidobacterium spp and L acidophilusgroup was detected while no significant differences wereobserved for Bacteroides spp Prevotella spp Enterococcusspp and C coccoides In a further paper of the same group[82] seven different intragenus bifidobacteria taxonomicclusters that were among the most common and abundantbifidobacteria species inhabiting the human gutwere targetedin the same samples It was found thatB adolescentisB breveB catenulatumpseudocatenulatum and B longum subsplongumwere always present in the group of subjects enrolledwhereas B bifidum and B longum subsp infantis were notIn spite of the large interindividual variability a significantincrease of B longum subsp infantis cell concentration wasobserved in the feces of volunteers after the wild blueberrydrink treatment which was attributed to the presence ofprebiotic (bifidogenic) molecules from blueberries possiblyfibers and glycosylated anthocyanins

In a study with postmenopausal women (119899 = 39)Clavel et al [83] found that isoflavone supplementationstimulated dominant microorganisms of the C coccoides-Erectale cluster Lactobacillus-Enterococcus group Faecalibac-terium prausnitzii subgroup and Bifidobacterium genus Itwas also suggested that the concentration of C coccoides-Erectale cluster was related to women capacity to excrete equolan intestinal metabolite from daidzein In two interventionstudies with whole grain breakfast cereals from wheat (119899 =31) and maize (119899 = 32) [84 85] the ingestion of both

products resulted in significant increases in fecal bifidobac-teria andor lactobacilli without changing the relative abun-dance of other dominant members of the gut microbiotaLittle or no changes were observed in the numbers of totalbacteria Bacteroides spp C histolyticumperfringens groupand Acetobacterium spp present in the feces However aswhole grains are good sources of dietary fiber it is difficult toascribe the observed effects only to the phenolic compoundspresent in these foods In this respect Cuervo et al [86] haverecently studied the correlations between the intake of fiberand polyphenols from diet and fecal microbiota compositionin a cohort of apparently healthy subjects Results showedthat the intake of soluble pectins and flavanones fromorangespresented a negative correlation with the levels of B coccoidesand C leptum By contrast the intake of white breadproviding hemicellulose and resistant starch was directlycorrelated with Lactobacillus

Finally another human trial (119899 = 16) carried out byJaquet et al [87] assessed the impact of a moderate con-sumption of instant coffee on the general composition ofthe human intestinal bacterial population Coffee bever-ages contain significant amounts of soluble fibre (mainlygalactomannans and arabinogalactan-proteins) and phenoliccompounds (chlorogenic acids) which arewell utilised by thehuman fecal microbiota It was observed that although fecalprofiles of the dominant microbiota were not significantlyaffected after the consumption of the coffee the populationof Bifidobacterium spp increased being the largest increaseobserved for those volunteers showing the lowest initialbifidobacteria levels

8 Conclusions

This review has tried to summarize the current knowledgein relation to the phenolic metabolism by gut microbiota andthemodulation of the gutmicrobiota by phenolic compoundsand polyphenol-rich dietary sourcesThere are evidences thatthe beneficial effects attribute to dietary polyphenols dependon their biotransformation by the gut microbiota Thereforeit is important to investigate the bacterial species impli-cated in the metabolism of dietary polyphenols and furtherresearch is still needed in relation to the resultant microbialmetabolites to ascertain their mechanisms of action Onthe other hand a great number of in vitro and in vivo (inanimals andhumans) studies showing the influence of dietarypolyphenols on gut-inhabiting bacteria have been publishedin recent years Although in vitro assays facilitate experimen-tation caution must be taken in extrapolating results to invivo situation as many factors are acting upon this processIn general in both in vitro and in vivo studies polyphenols orpolyphenol-rich sources have shown to influence the relativeabundance of different bacterial groups within the gut micro-biota reducing numbers of potential pathogens including Cperfringens and C histolyticum and certain Gram-negativeBacteroides spp and enhancing mainly beneficial Clostridiabifidobacteria and lactobacilli A better understanding of theinteraction between dietary polyphenols and gut microbiotathrough the emerging advances in high-throughput meta-genomic transcriptomic and proteomic approaches would

12 BioMed Research International

be essential in order to identify genes and micro-organismsinvolved in polyphenol (in)activation and conversion andthus to elucidate the implications of diet on the modulationof microbiota for delivering health benefits

Functional foods are considered to enhance the protectiveeffects against diseases derived from some food componentsIn the last decades dairy fermented foods have probablybeen one of the most-developed functional products andhave deserved intensive research In this expansion dairyfermented foods have been supplemented with fruits cerealsand other stuffs of plant origin all of which represent a highpercentage of the current market of the dairy industry Theseproducts have a healthy appeal which attracts consumersThus fruit juicesconcentrates and prepared fruits (in theform of pieces pulp and even flour) have been successfullyincorporated in dairy fermented foods as sources of prebioticfibers and phytochemicals Among these phytochemicalspresent in plant-derived foods polyphenols have gainedmuch interest due to their diverse potential beneficial effectsin human health The supplementation of dairy fermentedproducts with rich-polyphenolic stuffs (phenolic extractsphenolic-enriched fractions etc) seems to be an effectivetechnological option to improve the benefits of these productsin the balance of the intestinal microbiota due not only to theaction of the probiotics but also to the potential modulationeffects exerted by polyphenols as it has been described in thisreview Further research in this area will aim to accomplishthe benefits of both probiotic strains and polyphenols inrelation to gut health

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors of this review were funded by the SpanishMINECO through different projects (AGL2012-40172-C02-01 AGL2010-17499 and BFU2012-35228) and the CON-SOLIDER INGENIO 2010 programme (project FUN-C-FOOD CSD2007-063) as well as Comunidad de Madrid(project ALIBIRD P2009AGR-1469) Montserrat Duenaswould like to thank the Spanish ldquoRamon y Cajalrdquo Programmefor a contract

References

[1] S E Power P W OrsquoToole C Stanton R P Ross and GF Fitzgerald ldquoIntestinal microbiota diet and healthrdquo BritishJournal of Nutrition vol 111 no 3 pp 387ndash402 2014

[2] PDeCruz L Prideaux JWagner et al ldquoCharacterization of thegastrointestinal microbiota in health and inflammatory boweldiseaserdquo Inflammatory Bowel Diseases vol 18 no 2 pp 372ndash390 2012

[3] A Kramer S Bekeschus B M Broker H Schleibinger BRazavi and O Assadian ldquoMaintaining health by balancingmicrobial exposure and prevention of infection the hygienehypothesis versus the hypothesis of early immune challengerdquoJournal of Hospital Infection vol 83 no 1 pp S29ndashS34 2013

[4] M Rescigno ldquoIntestinal microbiota and its effects on theimmune systemrdquo Cellular Microbiology vol 16 no 7 pp 1004ndash1013 2014

[5] M G L Hertog E J M Feskens P C H HollmanM B Katanand D Kromhout ldquoDietary antioxidant flavonoids and risk ofcoronary heart disease the Zutphen Elderly StudyrdquoThe Lancetvol 342 no 8878 pp 1007ndash1011 1993

[6] I C W Arts and P C H Hollman ldquoPolyphenols and diseaserisk in epidemiologic studiesrdquoThe American Journal of ClinicalNutrition vol 81 no 1 pp 317Sndash325S 2009

[7] D del Rio A Rodriguez-Mateos J P E Spencer M TognoliniG Borges and A Crozier ldquoDietary (poly)phenolics in humanhealth structures bioavailability and evidence of protectiveeffects against chronic diseasesrdquo Antioxidants amp Redox Signal-ing vol 18 no 14 pp 1818ndash1892 2013

[8] F Perez-Vizcaino and J Duarte ldquoFlavonols and cardiovasculardiseaserdquo Molecular Aspects of Medicine vol 31 no 6 pp 478ndash494 2010

[9] J P E Spencer K Vafeiadou R J Williams and D VauzourldquoNeuroinflammation modulation by flavonoids and mecha-nisms of actionrdquo Molecular Aspects of Medicine vol 33 no 1pp 83ndash97 2012

[10] J M Laparra and Y Sanz ldquoInteractions of gut microbiota withfunctional food components and nutraceuticalsrdquo Pharmacolog-ical Research vol 61 no 3 pp 219ndash225 2010

[11] X He M L Marco and C M Slupsky ldquoEmerging aspects offood and nutrition on gut microbiotardquo Journal of Agriculturaland Food Chemistry vol 61 no 40 pp 9559ndash9574 2013

[12] D Hervert-Hernandez and I Goni ldquoDietary polyphenols andhuman gut microbiota a reviewrdquo Food Reviews Internationalvol 27 no 2 pp 154ndash169 2011

[13] K M Tuohy L Conterno M Gasperotti and R Viola ldquoUp-regulating the human intestinal microbiome using whole plantfoods polyphenols andor fiberrdquo Journal of Agricultural andFood Chemistry vol 60 no 36 pp 8776ndash8782 2012

[14] U Etxeberria A Fernandez-Quintela F I Milagro L AguirreJ A Martınez and M P Portillo ldquoImpact of polyphenols andpolyphenol-rich dietary sources on gut microbiota composi-tionrdquo Journal of Agricultural and Food Chemistry vol 61 no 40pp 9517ndash9533 2013

[15] F Cardona C Andres-Lacueva S Tulipani F J Tinahonesand M I Queipo-Ortuno ldquoBenefits of polyphenols on gutmicrobiota and implications in human healthrdquo Journal ofNutritional Biochemistry vol 24 no 8 pp 1415ndash1422 2013

[16] M V Selma J C Espın and F A Tomas-Barberan ldquoInteractionbetween phenolics and gut microbiota role in human healthrdquoJournal of Agricultural and Food Chemistry vol 57 no 15 pp6485ndash6501 2009

[17] T RequenaMMonagasM A Pozo-Bayon et al ldquoPerspectivesof the potential implications ofwine polyphenols on humanoraland gut microbiotardquo Trends in Food Science amp Technology vol21 no 7 pp 332ndash344 2010

[18] J Van Duynhoven E E Vaughan F van Dorsten et alldquoInteractions of black tea polyphenols with human gut micro-biota implications for gut and cardiovascular health1-4rdquo TheAmerican Journal of Clinical Nutrition vol 98 no 6 pp 1631Sndash1641S 2013

[19] SMoco F-P JMartin and S Rezzi ldquoMetabolomics view on gutmicrobiome modulation by polyphenol-rich foodsrdquo Journal ofProteome Research vol 11 no 10 pp 4781ndash4790 2012

BioMed Research International 13

[20] R K Buddington and P T Sangild ldquoCompanion animalssymposium development of the mammalian gastrointestinaltract the resident microbiota and the role of diet in early liferdquoJournal of Animal Science vol 89 no 5 pp 1506ndash1519 2011

[21] K Tiihonen A C Ouwehand and N Rautonen ldquoHumanintestinal microbiota and healthy ageingrdquo Ageing ResearchReviews vol 9 no 2 pp 107ndash116 2010

[22] D Mariat O Firmesse F Levenez et al ldquoThe firmicutesbacteroidetes ratio of the human microbiota changes with agerdquoBMCMicrobiology vol 9 article 123 2009

[23] M Arumugam J Raes E Pelletier et al ldquoEnterotypes of thehuman gutmicrobiomerdquoNature vol 473 no 7346 pp 174ndash1802011

[24] G D Wu J Chen C Hoffmann et al ldquoLinking long-termdietary patterns with gut microbial enterotypesrdquo Science vol334 no 6052 pp 105ndash108 2011

[25] I B JefferyM J Claesson PWOrsquoToole and F Shanahan ldquoCat-egorization of the gut microbiota enterotypes or gradientsrdquoNature Reviews Microbiology vol 10 no 9 pp 591ndash592 2012

[26] WM de Vos andM Nieuwdorp ldquoGenomics a gut predictionrdquoNature vol 498 no 7452 pp 48ndash49 2013

[27] P B Eckburg E M Bik C N Bernstein et al ldquoMicrobiologydiversity of the human intestinal microbial florardquo Science vol308 no 5728 pp 1635ndash1638 2005

[28] E G Zoetendal C T Collier S Koike R I Mackie and H RGaskins ldquoMolecular ecological analysis of the gastrointestinalmicrobiota a reviewrdquo Journal of Nutrition vol 134 no 2 pp465ndash472 2004

[29] M H Fraher PW OrsquoToole and E MM Quigley ldquoTechniquesused to characterize the gut microbiota a guide for the clini-cianrdquo Nature Reviews Gastroenterology and Hepatology vol 9no 6 pp 312ndash322 2012

[30] R A Kemperman S Bolca L C Roger and E E VaughanldquoNovel approaches for analysing gut microbes and dietarypolyphenols challenges and opportunitiesrdquo Microbiology vol156 no 11 pp 3224ndash3231 2010

[31] R A Kemperman G Gross S Mondot et al ldquoImpact ofpolyphenols from black tea and red winegrape juice on a gutmodel microbiomerdquo Food Research International vol 53 no 2pp 659ndash669 2013

[32] M N Clifford ldquoDiet-derived phenols in plasma and tissues andtheir implications for healthrdquo Planta Medica vol 70 no 12 pp1103ndash1114 2004

[33] A Crozier D del Rio and M N Clifford ldquoBioavailability ofdietary flavonoids and phenolic compoundsrdquoMolecular Aspectsof Medicine vol 31 no 6 pp 446ndash467 2010

[34] A J Day M S Dupont S Ridley et al ldquoDeglycosylation offlavonoid and isoflavonoid glycosides by human small intestineand liver beta-glucosidase activityrdquo FEBS Letters vol 436 no 1pp 71ndash75 1998

[35] A J Day F J Canada J C Dıaz et al ldquoDietary flavonoid andisoflavone glycosides are hydrolysed by the lactase site of lactasephlorizin hydrolaserdquo FEBS Letters vol 468 no 2-3 pp 166ndash1702000

[36] A Scalbert and G Williamson ldquoDietary intake and bioavail-ability of polyphenolsrdquo Journal of Nutrition vol 130 no 8 pp2073Sndash2085S 2000

[37] A R Rechner G Kuhnle H Hu et al ldquoThe metabolism ofdietary polyphenols and the relevance to circulating levels ofconjugated metabolitesrdquo Free Radical Research vol 36 no 11pp 1229ndash1241 2002

[38] A-M Aura K A OrsquoLeary G Williamson et al ldquoQuercetinderivatives are deconjugated and converted to hydroxypheny-lacetic acids but not methylated by human fecal flora in vitrordquoJournal of Agricultural and Food Chemistry vol 50 no 6 pp1725ndash1730 2002

[39] A-M Aura ldquoMicrobial metabolism of dietary phenolic com-pounds in the colonrdquo Phytochemistry Reviews vol 7 no 3 pp407ndash429 2008

[40] M Monagas M Urpi-Sarda F Sanchez-Patan et al ldquoInsightsinto themetabolism andmicrobial biotransformation of dietaryflavan-3-ols and the bioactivity of their metabolitesrdquo Food andFunction vol 1 no 3 pp 233ndash253 2010

[41] GWilliamson andMNClifford ldquoColonicmetabolites of berrypolyphenols the missing link to biological activityrdquo BritishJournal of Nutrition vol 104 no 3 pp S48ndashS66 2010

[42] D M Jacobs E Gaudier J van Duynhoven and E E VaughanldquoNon-digestible food ingredients colonic microbiota and theimpact on gut health and immunity a role for metabolomicsrdquoCurrent Drug Metabolism vol 10 no 1 pp 41ndash54 2009

[43] S Bolca S Possemiers V Maervoet et al ldquoMicrobial anddietary factors associatedwith the 8-prenylnaringenin producerphenotype a dietary intervention trial with fifty healthy post-menopausal Caucasian womenrdquo British Journal of Nutritionvol 98 no 5 pp 950ndash959 2007

[44] X Tzounis J Vulevic G G C Kuhnle et al ldquoFlavanolmonomer-induced changes to the human faecal microflorardquoBritish Journal of Nutrition vol 99 no 4 pp 782ndash792 2008

[45] M Hidalgo M J Oruna-Concha S Kolida et al ldquoMetabolismof anthocyanins by human gut microflora and their influenceon gut bacterial growthrdquo Journal of Agricultural and FoodChemistry vol 60 no 15 pp 3882ndash3890 2012

[46] A L Molan M A Lila J Mawson and S De ldquoIn vitroand in vivo evaluation of the prebiotic activity of water-soluble blueberry extractsrdquo World Journal of Microbiology andBiotechnology vol 25 no 7 pp 1243ndash1249 2009

[47] D Bialonska P Ramnani S G Kasimsetty K R Muntha GR Gibson and D Ferreira ldquoThe influence of pomegranate by-product and punicalagins on selected groups of human intesti-nal microbiotardquo International Journal of FoodMicrobiology vol140 no 2-3 pp 175ndash182 2010

[48] G Mandalari R M Faulks C Bisignano K W Waldron ANarbad and M S J Wickham ldquoIn vitro evaluation of theprebiotic properties of almond skins (Amygdalus communisL)rdquoFEMS Microbiology Letters vol 304 no 2 pp 116ndash122 2010

[49] V Fogliano M L Corollaro P Vitaglione et al ldquoIn vitro bioac-cessibility and gut biotransformation of polyphenols present inthe water-insoluble cocoa fractionrdquoMolecular Nutritionamp FoodResearch vol 55 supplement 1 pp S44ndashS55 2011

[50] M J Pozuelo A Agis-Torres D Hervert-Hernandez etal ldquoGrape antioxidant dietary fiber stimulates Lactobacillusgrowth in rat cecumrdquo Journal of Food Science vol 77 no 2 ppH59ndashH62 2012

[51] C Cueva F Sanchez-Patan M Monagas et al ldquoIn vitrofermentation of grape seed flavan-3-ol fractions by humanfaecal microbiota changes in microbial groups and phenolicmetabolitesrdquo FEMSMicrobiology Ecology vol 83 no 3 pp 792ndash805 2013

[52] F Sanchez-Patan C CuevaMMonagas et al ldquoIn vitro fermen-tation of a red wine extract by human gut microbiota changesin microbial groups and formation of phenolic metabolitesrdquoJournal of Agricultural and Food Chemistry vol 60 no 9 pp2136ndash2147 2012

14 BioMed Research International

[53] E Barroso F Sanchez-Patan P J Martın-Alvarez et al ldquoLacto-bacillus plantarum IFPL935 favors the initial metabolism of redwine polyphenols when added to a colonic microbiotardquo Journalof Agricultural and Food Chemistry vol 61 no 42 pp 10163ndash10172 2013

[54] G R Gibson J H Cummings and G T Macfarlane ldquoUse ofa three-stage continuous culture system to study the effect ofmucin on dissimilatory sulfate reduction and methanogenesisby mixed populations of human gut bacteriardquo Applied andEnvironmentalMicrobiology vol 54 no 11 pp 2750ndash2755 1988

[55] KMollyMVandeWoestyne andWVerstraete ldquoDevelopmentof a 5-step multi-chamber reactor as a simulation of thehuman intestinal microbial ecosystemrdquo Applied Microbiologyand Biotechnology vol 39 no 2 pp 254ndash258 1993

[56] M Minekus M Smeets-Peeters A Bernalier et al ldquoAcomputer-controlled system to simulate conditions of thelarge intestine with peristaltic mixing water absorption andabsorption of fermentation productsrdquoAppliedMicrobiology andBiotechnology vol 53 no 1 pp 108ndash114 1999

[57] PDeBoever BDeplancke andWVerstraete ldquoFermentation bygut microbiota cultured in a simulator of the human intestinalmicrobial ecosystem is improved by supplementing a soygermpowderrdquo Journal of Nutrition vol 130 no 10 pp 2599ndash26062000

[58] C S Yang X Wang G Lu and S C Picinich ldquoCancerprevention by tea animal studies molecular mechanisms andhuman relevancerdquoNature Reviews Cancer vol 9 no 6 pp 429ndash439 2009

[59] R E Ley F Backhed P Turnbaugh C A Lozupone R DKnight and J I Gordon ldquoObesity alters gut microbial ecologyrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 102 no 31 pp 11070ndash11075 2005

[60] H Hara N Orita S Hatano et al ldquoEffect of tea polyphenols onfecal flora and fecal metabolic products of pigsrdquo The Journal ofVeterinary Medical Science vol 57 no 1 pp 45ndash49 1995

[61] N Ishihara D-C Chu S Akachi and L R Juneja ldquoImprove-ment of intestinal microflora balance and prevention of diges-tive and respiratory organ diseases in calves by green teaextractsrdquo Livestock Production Science vol 68 no 2-3 pp 217ndash229 2001

[62] P Dolara C Luceri C De Filippo et al ldquoRed wine polyphenolsinfluence carcinogenesis intestinal microflora oxidative dam-age and gene expression profiles of colonicmucosa in F344 ratsrdquoMutation Research-Fundamental and Molecular Mechanisms ofMutagenesis vol 591 no 1-2 pp 237ndash246 2005

[63] S Sembries G Dongowski K Mehrlander F Will and HDietrich ldquoPhysiological effects of extraction juices from applegrape and red beet pomaces in ratsrdquo Journal of Agricultural andFood Chemistry vol 54 no 26 pp 10269ndash10280 2006

[64] S Sembries G Dongowski G Jacobasch K Mehrlander FWill andH Dietrich ldquoEffects of dietary fibre-rich juice colloidsfrom apple pomace extraction juices on intestinal fermentationproducts and microbiota in ratsrdquo British Journal of Nutritionvol 90 no 3 pp 607ndash615 2003

[65] A Viveros S Chamorro M Pizarro I Arija C Centeno andA Brenes ldquoEffects of dietary polyphenol-rich grape productson intestinal microflora and gut morphology in broiler chicksrdquoPoultry Science vol 90 no 3 pp 566ndash578 2011

[66] A H Smith and R I Mackie ldquoEffect of condensed tannins onbacterial diversity andmetabolic activity in the rat gastrointesti-nal tractrdquo Applied and Environmental Microbiology vol 70 no2 pp 1104ndash1115 2004

[67] M Massot-Cladera T Perez-Berezo A Franch M Castelland F J Perez-Cano ldquoCocoa modulatory effect on rat faecalmicrobiota and colonic crosstalkrdquo Archives of Biochemistry andBiophysics vol 527 no 2 pp 105ndash112 2012

[68] M Larrosa M J Yanez-Gascon M V Selma et al ldquoEffectof a low dose of dietary resveratrol on colon microbiotainflammation and tissue damage in a DSS-induced colitis ratmodelrdquo Journal of Agricultural and Food Chemistry vol 57 no6 pp 2211ndash2220 2009

[69] A-L Molan Z Liu andM Kruger ldquoThe ability of blackcurrantextracts to positively modulate key markers of gastrointestinalfunction in ratsrdquoWorld Journal ofMicrobiologyampBiotechnologyvol 26 no 10 pp 1735ndash1743 2010

[70] A Lacombe R W Li D Klimis-Zacas et al ldquoLowbush wildblueberries have the potential to modify gut microbiota andxenobiotic metabolism in the rat colonrdquo PLoS ONE vol 8 no6 Article ID e67497 2013

[71] R Saad M R Rizkallah and R K Aziz ldquoGut Pharmacomicro-biomics the tip of an iceberg of complex interactions betweendrugs and gut-associated microbesrdquo Gut Pathogens vol 4 no1 article 16 2012

[72] E J J Van Velzen J A Westerhuis J P M van Duynhovenet al ldquoMultilevel data analysis of a crossover designed humannutritional intervention studyrdquo Journal of Proteome Researchvol 7 no 10 pp 4483ndash4491 2008

[73] T Okubo N Ishihara H Takahashi et al ldquoEffects of partiallyhydrolyzed guar gum intake on human intestinal microfloraand itsmetabolismrdquoBioscience Biotechnology andBiochemistryvol 58 no 8 pp 1364ndash1369 1994

[74] V Mai H A Katki H Harmsen et al ldquoEffects of a controlleddiet and black tea drinking on the fecalmicroflora compositionand the fecal bile acid profile of human volunteers in a double-blinded ramdomized feeding studyrdquo The Journal of Nutritionvol 134 no 2 pp 473ndash478 2004

[75] J-S Jin M Touyama T Hisada and Y Benno ldquoEffectsof green tea consumption on human fecal microbiota withspecial reference to Bifidobacterium speciesrdquoMicrobiology andImmunology vol 56 no 11 pp 729ndash739 2012

[76] J Yamakoshi S Tokutake M Kikuchi Y Kubota H Konishiand T Mitsuoka ldquoEffect of proantocyanidin -rich extract fromgrape seed on human fecal flora and fecalodorrdquo FASEB Journalvol 15 no 4 p A633 2001

[77] X Tzounis A Rodriguez-Mateos J Vulevic G R Gibson CKwik-Uribe and J P E Spencer ldquoPrebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomizedcontrolled double-blind crossover intervention studyrdquo TheAmerican Journal of Clinical Nutrition vol 93 no 1 pp 62ndash722011

[78] M I Queipo-Ortuno M Boto-Ordonez M Murri et alldquoInfluence of red wine polyphenols and ethanol on the gutmicrobiota ecology and biochemical biomarkersrdquo AmericanJournal of Clinical Nutrition vol 95 no 6 pp 1323ndash1334 2012

[79] K Shinohara Y Ohashi K Kawasumi A Terada and TFujisawa ldquoEffect of apple intake on fecal microbiota andmetabolites in humansrdquo Anaerobe vol 16 no 5 pp 510ndash5152010

[80] C I R Gill G J Mcdougall S Glidewell et al ldquoProfiling ofphenols in human fecal water after raspberry supplementationrdquoJournal of Agricultural and Food Chemistry vol 58 no 19 pp10389ndash10395 2010

[81] S Vendrame S Guglielmetti P Riso S Arioli D Klimis-Zacasand M Porrini ldquoSix-week consumption of a wild blueberry

BioMed Research International 15

powder drink increases Bifidobacteria in the human gutrdquoJournal of Agricultural and Food Chemistry vol 59 no 24 pp12815ndash12820 2011

[82] S Guglielmetti D Fracassetti V Taverniti et al ldquoDifferentialmodulation of human intestinal Bifidobacterium populationsafter consumption of a wild blueberry (Vaccinium angusti-folium) drinkrdquo Journal of Agricultural and Food Chemistry vol61 no 34 pp 8134ndash8140 2013

[83] T Clavel M Fallani P Lepage et al ldquoIsoflavones and func-tional foods alter the dominant intestinal microbiota in post-menopausal womenrdquo Journal of Nutrition vol 135 no 12 pp2786ndash2792 2005

[84] A Costabile A Klinder F Fava et al ldquoWhole-grain wheatbreakfast cereal has a prebiotic effect on the human gut micro-biota a double-blind placebo-controlled crossover studyrdquoBritish Journal of Nutrition vol 99 no 1 pp 110ndash120 2008

[85] A L Carvalho-Wells K Helmolz C Nodet et al ldquoDetermina-tion of the in vivo prebiotic potential of a maize-based wholegrain breakfast cereal a human feeding studyrdquo British Journalof Nutrition vol 104 no 9 pp 1353ndash1356 2010

[86] A Cuervo L Valdes N Salazar et al ldquoPilot study of diet andmicrobiota interactive associations of fibers and polyphenolswith human intestinal bacteriardquo Journal of Agricultural andFood Chemistry vol 62 no 23 pp 5330ndash5336 2014

[87] M Jaquet I Rochat J Moulin C Cavin and R BibilonildquoImpact of coffee consumption on the gut microbiota a humanvolunteer studyrdquo International Journal of FoodMicrobiology vol130 no 2 pp 117ndash121 2009

Submit your manuscripts athttpwwwhindawicom

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Page 9: Review Article A Survey of Modulation of Gut Microbiota by ...downloads.hindawi.com/journals/bmri/2015/850902.pdf · Review Article A Survey of Modulation of Gut Microbiota by Dietary

BioMed Research International 9

Table4Hum

aninterventio

nstu

dies

Reference

Volunteer

number

Phenolic

compo

undfood

Dose

Treatm

ent

duratio

nMicrobial

techniqu

ePo

pulatio

nincrease

Popu

latio

ndecrease

Noeffect

Oku

boetal

(1994)[73]

8Green

tea

(Sun

phenon

)04g

3tim

esper

day

4weeks

Platec

ount

Cperfr

ingens

Clostridium

spp

Yamakoshi

etal(2001)[76]

9Proantocyanidin-

richextractfrom

grapes

eeds

05g

day

6weeks

Platec

ount

Bifid

obacteriu

mspp

Enterobacteriaceae

Maietal

(200

4)[74]

15Blacktea

700m

gteas

olids5

times

perd

ay21

days

FISH

DGGE

Totalbacteria

Nochanges

Claveletal

(2005)

[83]

39Isofl

avon

es100m

gday

2mon

ths

TTGEFISH

Ccoccoides-E

rectale

grou

pBifid

obacteriu

mspp

Lactobacillus-

Enterococcus

spp

Faecalibacteriu

mprau

snitziisubgroup

Costabileetal

(2008)

[84]

31Who

legrainwheat

cereals

48gday

3weeks

FISH

Bifid

obacteria

Lactob

acilli

Totalbacteria

Bacteroidesspp

C

histo

lyticum

perfringens

grou

pAc

etobacteriu

mspp

Jaqu

etetal

(200

9)[87]

16Coff

ee3cupsday

3weeks

FISH

DGGE

Bifid

obacteriu

mspp

Carvalho

-Wellsetal

(2010)

[85]

32Who

legrainmaize

cereals

48gday

3weeks

FISH

Bifid

obacteria

Totalbacteria

Bacteroidesspp

C

histo

lyticum

perfringens

grou

pAc

etobacteriu

mspp

Gill

etal

(2010)

[80]

10Ra

spberrypu

ree

20gday

4days

PCR-DGGE

Nochangesinthep

rofileo

fcolonicb

acteria

Shinoh

arae

tal(2010)[79]

8Ap

ples

2applesday

2weeks

Platec

ount

Lactobacillus

spp

Streptococcusspp

En

terococcus

spp

Enterobacteriaceae

lecithinase-po

sitive

clostrid

iainclu

ding

Cperfr

ingens

Pseudomonas

spp

10 BioMed Research International

Table4Con

tinued

Reference

Volunteer

number

Phenolic

compo

undfood

Dose

Treatm

ent

duratio

nMicrobial

techniqu

ePo

pulatio

nincrease

Popu

latio

ndecrease

Noeffect

Tzou

nise

tal

(2011)[77]

22Cocoa

flavano

l494m

gday

29mgday

4weeks

FISH

Bifid

obacteriu

mspp

Lactobacillus

spp

Chisto

lyticum

perfringens

grou

p

Vend

ramee

tal(2011)[81]

15Wild

blueberry

drink

25gwild

blueberriesd

ay6weeks

qPCR

Bifid

obacteriu

mspp

Lacidophilus

Bacteroidesspp

Prevotellaspp

Enterococcus

spp

Ccoccoides

Queipo-

Ortun

oetal

(2012)

[78]

10Re

dwine

272m

Lday

20days

qPCR

Enterococcus

spp

Prevotellaspp

Bacteroides

Bifid

obacteriu

mspp

Bacteroidesu

niform

isEggerthella

lenta

Blautia

coccoides-E

rectaleg

roup

Clostridium

spp

Chisto

lyticum

group

Actin

obacteria

Jinetal(2012)

[75]

10Green

tea

1000

mLday

10days

T-RF

LPqP

CRBifid

obacteriu

mspp

Gug

lielm

ettiet

al(2013)[82]

15Wild

blueberries

drink

25gwild

blueberriesd

ay6weeks

qPCR

Blongum

subspinfantis

Cuervo

etal

(2014)

[86]

38

Dairy

prod

ucts

Fruits

Vegetables

Cereals

Food

intake

was

recorded

usingan

annu

alfood

frequ

ency

questio

nnaire

qPCR

Lactobacillus

Bcoccoides

Clep

tum

BioMed Research International 11

three consecutive periods After the red wine period thebacterial concentrations of proteobacteria fusobacteria Fir-micutes and Bacteroidetes markedly increased comparedwith the washout period significant increases in the num-ber of Bifidobacterium spp and Prevotella spp were alsoobserved However Lactobacillus spp Clostridium spp andC histolyticum group concentrations remained unchangedthroughout the study

In a small-scale observational study (119899 = 8) Shinoharaet al [79] found that the number of bifidobacteria in fecessignificantly increased during apple intake and the numbersof Lactobacillus spp Streptococcus spp and Enterococcusspp tended to increase On the contrary enterobacteriaand lecithinase-positive clostridia including C perfringensand Pseudomonas species tended to decrease Howeverthat study did not use culture-independent microbiologytechniques and suffered from the lack of a control groupAlso in relation to fruits another small human interventionstudy (119899 = 10) with raspberry puree [80] did not observestatistically significant alterations in the profile of colonicbacteria probably due to high interindividual variation infecal bacteria although the profiles of microbial metabolitesof raspberry polyphenols varied greatly between individualsindicating that the type of gut microbiota affects cataboliteprofiles released by bacteria in the colonThis lack of effect onthe intestinal microbiota after the intake of raspberry pureemight also be due to the short duration of the treatment aswell as the techniques employed to quantify the intestinalmicrobiota

Vendrame et al [81] studied the potential prebioticactivity of a drink elaborated fromwild blueberries especiallyrich in anthocyanins in a small intervention trial (119899 = 15) Asignificant increase in Bifidobacterium spp and L acidophilusgroup was detected while no significant differences wereobserved for Bacteroides spp Prevotella spp Enterococcusspp and C coccoides In a further paper of the same group[82] seven different intragenus bifidobacteria taxonomicclusters that were among the most common and abundantbifidobacteria species inhabiting the human gutwere targetedin the same samples It was found thatB adolescentisB breveB catenulatumpseudocatenulatum and B longum subsplongumwere always present in the group of subjects enrolledwhereas B bifidum and B longum subsp infantis were notIn spite of the large interindividual variability a significantincrease of B longum subsp infantis cell concentration wasobserved in the feces of volunteers after the wild blueberrydrink treatment which was attributed to the presence ofprebiotic (bifidogenic) molecules from blueberries possiblyfibers and glycosylated anthocyanins

In a study with postmenopausal women (119899 = 39)Clavel et al [83] found that isoflavone supplementationstimulated dominant microorganisms of the C coccoides-Erectale cluster Lactobacillus-Enterococcus group Faecalibac-terium prausnitzii subgroup and Bifidobacterium genus Itwas also suggested that the concentration of C coccoides-Erectale cluster was related to women capacity to excrete equolan intestinal metabolite from daidzein In two interventionstudies with whole grain breakfast cereals from wheat (119899 =31) and maize (119899 = 32) [84 85] the ingestion of both

products resulted in significant increases in fecal bifidobac-teria andor lactobacilli without changing the relative abun-dance of other dominant members of the gut microbiotaLittle or no changes were observed in the numbers of totalbacteria Bacteroides spp C histolyticumperfringens groupand Acetobacterium spp present in the feces However aswhole grains are good sources of dietary fiber it is difficult toascribe the observed effects only to the phenolic compoundspresent in these foods In this respect Cuervo et al [86] haverecently studied the correlations between the intake of fiberand polyphenols from diet and fecal microbiota compositionin a cohort of apparently healthy subjects Results showedthat the intake of soluble pectins and flavanones fromorangespresented a negative correlation with the levels of B coccoidesand C leptum By contrast the intake of white breadproviding hemicellulose and resistant starch was directlycorrelated with Lactobacillus

Finally another human trial (119899 = 16) carried out byJaquet et al [87] assessed the impact of a moderate con-sumption of instant coffee on the general composition ofthe human intestinal bacterial population Coffee bever-ages contain significant amounts of soluble fibre (mainlygalactomannans and arabinogalactan-proteins) and phenoliccompounds (chlorogenic acids) which arewell utilised by thehuman fecal microbiota It was observed that although fecalprofiles of the dominant microbiota were not significantlyaffected after the consumption of the coffee the populationof Bifidobacterium spp increased being the largest increaseobserved for those volunteers showing the lowest initialbifidobacteria levels

8 Conclusions

This review has tried to summarize the current knowledgein relation to the phenolic metabolism by gut microbiota andthemodulation of the gutmicrobiota by phenolic compoundsand polyphenol-rich dietary sourcesThere are evidences thatthe beneficial effects attribute to dietary polyphenols dependon their biotransformation by the gut microbiota Thereforeit is important to investigate the bacterial species impli-cated in the metabolism of dietary polyphenols and furtherresearch is still needed in relation to the resultant microbialmetabolites to ascertain their mechanisms of action Onthe other hand a great number of in vitro and in vivo (inanimals andhumans) studies showing the influence of dietarypolyphenols on gut-inhabiting bacteria have been publishedin recent years Although in vitro assays facilitate experimen-tation caution must be taken in extrapolating results to invivo situation as many factors are acting upon this processIn general in both in vitro and in vivo studies polyphenols orpolyphenol-rich sources have shown to influence the relativeabundance of different bacterial groups within the gut micro-biota reducing numbers of potential pathogens including Cperfringens and C histolyticum and certain Gram-negativeBacteroides spp and enhancing mainly beneficial Clostridiabifidobacteria and lactobacilli A better understanding of theinteraction between dietary polyphenols and gut microbiotathrough the emerging advances in high-throughput meta-genomic transcriptomic and proteomic approaches would

12 BioMed Research International

be essential in order to identify genes and micro-organismsinvolved in polyphenol (in)activation and conversion andthus to elucidate the implications of diet on the modulationof microbiota for delivering health benefits

Functional foods are considered to enhance the protectiveeffects against diseases derived from some food componentsIn the last decades dairy fermented foods have probablybeen one of the most-developed functional products andhave deserved intensive research In this expansion dairyfermented foods have been supplemented with fruits cerealsand other stuffs of plant origin all of which represent a highpercentage of the current market of the dairy industry Theseproducts have a healthy appeal which attracts consumersThus fruit juicesconcentrates and prepared fruits (in theform of pieces pulp and even flour) have been successfullyincorporated in dairy fermented foods as sources of prebioticfibers and phytochemicals Among these phytochemicalspresent in plant-derived foods polyphenols have gainedmuch interest due to their diverse potential beneficial effectsin human health The supplementation of dairy fermentedproducts with rich-polyphenolic stuffs (phenolic extractsphenolic-enriched fractions etc) seems to be an effectivetechnological option to improve the benefits of these productsin the balance of the intestinal microbiota due not only to theaction of the probiotics but also to the potential modulationeffects exerted by polyphenols as it has been described in thisreview Further research in this area will aim to accomplishthe benefits of both probiotic strains and polyphenols inrelation to gut health

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors of this review were funded by the SpanishMINECO through different projects (AGL2012-40172-C02-01 AGL2010-17499 and BFU2012-35228) and the CON-SOLIDER INGENIO 2010 programme (project FUN-C-FOOD CSD2007-063) as well as Comunidad de Madrid(project ALIBIRD P2009AGR-1469) Montserrat Duenaswould like to thank the Spanish ldquoRamon y Cajalrdquo Programmefor a contract

References

[1] S E Power P W OrsquoToole C Stanton R P Ross and GF Fitzgerald ldquoIntestinal microbiota diet and healthrdquo BritishJournal of Nutrition vol 111 no 3 pp 387ndash402 2014

[2] PDeCruz L Prideaux JWagner et al ldquoCharacterization of thegastrointestinal microbiota in health and inflammatory boweldiseaserdquo Inflammatory Bowel Diseases vol 18 no 2 pp 372ndash390 2012

[3] A Kramer S Bekeschus B M Broker H Schleibinger BRazavi and O Assadian ldquoMaintaining health by balancingmicrobial exposure and prevention of infection the hygienehypothesis versus the hypothesis of early immune challengerdquoJournal of Hospital Infection vol 83 no 1 pp S29ndashS34 2013

[4] M Rescigno ldquoIntestinal microbiota and its effects on theimmune systemrdquo Cellular Microbiology vol 16 no 7 pp 1004ndash1013 2014

[5] M G L Hertog E J M Feskens P C H HollmanM B Katanand D Kromhout ldquoDietary antioxidant flavonoids and risk ofcoronary heart disease the Zutphen Elderly StudyrdquoThe Lancetvol 342 no 8878 pp 1007ndash1011 1993

[6] I C W Arts and P C H Hollman ldquoPolyphenols and diseaserisk in epidemiologic studiesrdquoThe American Journal of ClinicalNutrition vol 81 no 1 pp 317Sndash325S 2009

[7] D del Rio A Rodriguez-Mateos J P E Spencer M TognoliniG Borges and A Crozier ldquoDietary (poly)phenolics in humanhealth structures bioavailability and evidence of protectiveeffects against chronic diseasesrdquo Antioxidants amp Redox Signal-ing vol 18 no 14 pp 1818ndash1892 2013

[8] F Perez-Vizcaino and J Duarte ldquoFlavonols and cardiovasculardiseaserdquo Molecular Aspects of Medicine vol 31 no 6 pp 478ndash494 2010

[9] J P E Spencer K Vafeiadou R J Williams and D VauzourldquoNeuroinflammation modulation by flavonoids and mecha-nisms of actionrdquo Molecular Aspects of Medicine vol 33 no 1pp 83ndash97 2012

[10] J M Laparra and Y Sanz ldquoInteractions of gut microbiota withfunctional food components and nutraceuticalsrdquo Pharmacolog-ical Research vol 61 no 3 pp 219ndash225 2010

[11] X He M L Marco and C M Slupsky ldquoEmerging aspects offood and nutrition on gut microbiotardquo Journal of Agriculturaland Food Chemistry vol 61 no 40 pp 9559ndash9574 2013

[12] D Hervert-Hernandez and I Goni ldquoDietary polyphenols andhuman gut microbiota a reviewrdquo Food Reviews Internationalvol 27 no 2 pp 154ndash169 2011

[13] K M Tuohy L Conterno M Gasperotti and R Viola ldquoUp-regulating the human intestinal microbiome using whole plantfoods polyphenols andor fiberrdquo Journal of Agricultural andFood Chemistry vol 60 no 36 pp 8776ndash8782 2012

[14] U Etxeberria A Fernandez-Quintela F I Milagro L AguirreJ A Martınez and M P Portillo ldquoImpact of polyphenols andpolyphenol-rich dietary sources on gut microbiota composi-tionrdquo Journal of Agricultural and Food Chemistry vol 61 no 40pp 9517ndash9533 2013

[15] F Cardona C Andres-Lacueva S Tulipani F J Tinahonesand M I Queipo-Ortuno ldquoBenefits of polyphenols on gutmicrobiota and implications in human healthrdquo Journal ofNutritional Biochemistry vol 24 no 8 pp 1415ndash1422 2013

[16] M V Selma J C Espın and F A Tomas-Barberan ldquoInteractionbetween phenolics and gut microbiota role in human healthrdquoJournal of Agricultural and Food Chemistry vol 57 no 15 pp6485ndash6501 2009

[17] T RequenaMMonagasM A Pozo-Bayon et al ldquoPerspectivesof the potential implications ofwine polyphenols on humanoraland gut microbiotardquo Trends in Food Science amp Technology vol21 no 7 pp 332ndash344 2010

[18] J Van Duynhoven E E Vaughan F van Dorsten et alldquoInteractions of black tea polyphenols with human gut micro-biota implications for gut and cardiovascular health1-4rdquo TheAmerican Journal of Clinical Nutrition vol 98 no 6 pp 1631Sndash1641S 2013

[19] SMoco F-P JMartin and S Rezzi ldquoMetabolomics view on gutmicrobiome modulation by polyphenol-rich foodsrdquo Journal ofProteome Research vol 11 no 10 pp 4781ndash4790 2012

BioMed Research International 13

[20] R K Buddington and P T Sangild ldquoCompanion animalssymposium development of the mammalian gastrointestinaltract the resident microbiota and the role of diet in early liferdquoJournal of Animal Science vol 89 no 5 pp 1506ndash1519 2011

[21] K Tiihonen A C Ouwehand and N Rautonen ldquoHumanintestinal microbiota and healthy ageingrdquo Ageing ResearchReviews vol 9 no 2 pp 107ndash116 2010

[22] D Mariat O Firmesse F Levenez et al ldquoThe firmicutesbacteroidetes ratio of the human microbiota changes with agerdquoBMCMicrobiology vol 9 article 123 2009

[23] M Arumugam J Raes E Pelletier et al ldquoEnterotypes of thehuman gutmicrobiomerdquoNature vol 473 no 7346 pp 174ndash1802011

[24] G D Wu J Chen C Hoffmann et al ldquoLinking long-termdietary patterns with gut microbial enterotypesrdquo Science vol334 no 6052 pp 105ndash108 2011

[25] I B JefferyM J Claesson PWOrsquoToole and F Shanahan ldquoCat-egorization of the gut microbiota enterotypes or gradientsrdquoNature Reviews Microbiology vol 10 no 9 pp 591ndash592 2012

[26] WM de Vos andM Nieuwdorp ldquoGenomics a gut predictionrdquoNature vol 498 no 7452 pp 48ndash49 2013

[27] P B Eckburg E M Bik C N Bernstein et al ldquoMicrobiologydiversity of the human intestinal microbial florardquo Science vol308 no 5728 pp 1635ndash1638 2005

[28] E G Zoetendal C T Collier S Koike R I Mackie and H RGaskins ldquoMolecular ecological analysis of the gastrointestinalmicrobiota a reviewrdquo Journal of Nutrition vol 134 no 2 pp465ndash472 2004

[29] M H Fraher PW OrsquoToole and E MM Quigley ldquoTechniquesused to characterize the gut microbiota a guide for the clini-cianrdquo Nature Reviews Gastroenterology and Hepatology vol 9no 6 pp 312ndash322 2012

[30] R A Kemperman S Bolca L C Roger and E E VaughanldquoNovel approaches for analysing gut microbes and dietarypolyphenols challenges and opportunitiesrdquo Microbiology vol156 no 11 pp 3224ndash3231 2010

[31] R A Kemperman G Gross S Mondot et al ldquoImpact ofpolyphenols from black tea and red winegrape juice on a gutmodel microbiomerdquo Food Research International vol 53 no 2pp 659ndash669 2013

[32] M N Clifford ldquoDiet-derived phenols in plasma and tissues andtheir implications for healthrdquo Planta Medica vol 70 no 12 pp1103ndash1114 2004

[33] A Crozier D del Rio and M N Clifford ldquoBioavailability ofdietary flavonoids and phenolic compoundsrdquoMolecular Aspectsof Medicine vol 31 no 6 pp 446ndash467 2010

[34] A J Day M S Dupont S Ridley et al ldquoDeglycosylation offlavonoid and isoflavonoid glycosides by human small intestineand liver beta-glucosidase activityrdquo FEBS Letters vol 436 no 1pp 71ndash75 1998

[35] A J Day F J Canada J C Dıaz et al ldquoDietary flavonoid andisoflavone glycosides are hydrolysed by the lactase site of lactasephlorizin hydrolaserdquo FEBS Letters vol 468 no 2-3 pp 166ndash1702000

[36] A Scalbert and G Williamson ldquoDietary intake and bioavail-ability of polyphenolsrdquo Journal of Nutrition vol 130 no 8 pp2073Sndash2085S 2000

[37] A R Rechner G Kuhnle H Hu et al ldquoThe metabolism ofdietary polyphenols and the relevance to circulating levels ofconjugated metabolitesrdquo Free Radical Research vol 36 no 11pp 1229ndash1241 2002

[38] A-M Aura K A OrsquoLeary G Williamson et al ldquoQuercetinderivatives are deconjugated and converted to hydroxypheny-lacetic acids but not methylated by human fecal flora in vitrordquoJournal of Agricultural and Food Chemistry vol 50 no 6 pp1725ndash1730 2002

[39] A-M Aura ldquoMicrobial metabolism of dietary phenolic com-pounds in the colonrdquo Phytochemistry Reviews vol 7 no 3 pp407ndash429 2008

[40] M Monagas M Urpi-Sarda F Sanchez-Patan et al ldquoInsightsinto themetabolism andmicrobial biotransformation of dietaryflavan-3-ols and the bioactivity of their metabolitesrdquo Food andFunction vol 1 no 3 pp 233ndash253 2010

[41] GWilliamson andMNClifford ldquoColonicmetabolites of berrypolyphenols the missing link to biological activityrdquo BritishJournal of Nutrition vol 104 no 3 pp S48ndashS66 2010

[42] D M Jacobs E Gaudier J van Duynhoven and E E VaughanldquoNon-digestible food ingredients colonic microbiota and theimpact on gut health and immunity a role for metabolomicsrdquoCurrent Drug Metabolism vol 10 no 1 pp 41ndash54 2009

[43] S Bolca S Possemiers V Maervoet et al ldquoMicrobial anddietary factors associatedwith the 8-prenylnaringenin producerphenotype a dietary intervention trial with fifty healthy post-menopausal Caucasian womenrdquo British Journal of Nutritionvol 98 no 5 pp 950ndash959 2007

[44] X Tzounis J Vulevic G G C Kuhnle et al ldquoFlavanolmonomer-induced changes to the human faecal microflorardquoBritish Journal of Nutrition vol 99 no 4 pp 782ndash792 2008

[45] M Hidalgo M J Oruna-Concha S Kolida et al ldquoMetabolismof anthocyanins by human gut microflora and their influenceon gut bacterial growthrdquo Journal of Agricultural and FoodChemistry vol 60 no 15 pp 3882ndash3890 2012

[46] A L Molan M A Lila J Mawson and S De ldquoIn vitroand in vivo evaluation of the prebiotic activity of water-soluble blueberry extractsrdquo World Journal of Microbiology andBiotechnology vol 25 no 7 pp 1243ndash1249 2009

[47] D Bialonska P Ramnani S G Kasimsetty K R Muntha GR Gibson and D Ferreira ldquoThe influence of pomegranate by-product and punicalagins on selected groups of human intesti-nal microbiotardquo International Journal of FoodMicrobiology vol140 no 2-3 pp 175ndash182 2010

[48] G Mandalari R M Faulks C Bisignano K W Waldron ANarbad and M S J Wickham ldquoIn vitro evaluation of theprebiotic properties of almond skins (Amygdalus communisL)rdquoFEMS Microbiology Letters vol 304 no 2 pp 116ndash122 2010

[49] V Fogliano M L Corollaro P Vitaglione et al ldquoIn vitro bioac-cessibility and gut biotransformation of polyphenols present inthe water-insoluble cocoa fractionrdquoMolecular Nutritionamp FoodResearch vol 55 supplement 1 pp S44ndashS55 2011

[50] M J Pozuelo A Agis-Torres D Hervert-Hernandez etal ldquoGrape antioxidant dietary fiber stimulates Lactobacillusgrowth in rat cecumrdquo Journal of Food Science vol 77 no 2 ppH59ndashH62 2012

[51] C Cueva F Sanchez-Patan M Monagas et al ldquoIn vitrofermentation of grape seed flavan-3-ol fractions by humanfaecal microbiota changes in microbial groups and phenolicmetabolitesrdquo FEMSMicrobiology Ecology vol 83 no 3 pp 792ndash805 2013

[52] F Sanchez-Patan C CuevaMMonagas et al ldquoIn vitro fermen-tation of a red wine extract by human gut microbiota changesin microbial groups and formation of phenolic metabolitesrdquoJournal of Agricultural and Food Chemistry vol 60 no 9 pp2136ndash2147 2012

14 BioMed Research International

[53] E Barroso F Sanchez-Patan P J Martın-Alvarez et al ldquoLacto-bacillus plantarum IFPL935 favors the initial metabolism of redwine polyphenols when added to a colonic microbiotardquo Journalof Agricultural and Food Chemistry vol 61 no 42 pp 10163ndash10172 2013

[54] G R Gibson J H Cummings and G T Macfarlane ldquoUse ofa three-stage continuous culture system to study the effect ofmucin on dissimilatory sulfate reduction and methanogenesisby mixed populations of human gut bacteriardquo Applied andEnvironmentalMicrobiology vol 54 no 11 pp 2750ndash2755 1988

[55] KMollyMVandeWoestyne andWVerstraete ldquoDevelopmentof a 5-step multi-chamber reactor as a simulation of thehuman intestinal microbial ecosystemrdquo Applied Microbiologyand Biotechnology vol 39 no 2 pp 254ndash258 1993

[56] M Minekus M Smeets-Peeters A Bernalier et al ldquoAcomputer-controlled system to simulate conditions of thelarge intestine with peristaltic mixing water absorption andabsorption of fermentation productsrdquoAppliedMicrobiology andBiotechnology vol 53 no 1 pp 108ndash114 1999

[57] PDeBoever BDeplancke andWVerstraete ldquoFermentation bygut microbiota cultured in a simulator of the human intestinalmicrobial ecosystem is improved by supplementing a soygermpowderrdquo Journal of Nutrition vol 130 no 10 pp 2599ndash26062000

[58] C S Yang X Wang G Lu and S C Picinich ldquoCancerprevention by tea animal studies molecular mechanisms andhuman relevancerdquoNature Reviews Cancer vol 9 no 6 pp 429ndash439 2009

[59] R E Ley F Backhed P Turnbaugh C A Lozupone R DKnight and J I Gordon ldquoObesity alters gut microbial ecologyrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 102 no 31 pp 11070ndash11075 2005

[60] H Hara N Orita S Hatano et al ldquoEffect of tea polyphenols onfecal flora and fecal metabolic products of pigsrdquo The Journal ofVeterinary Medical Science vol 57 no 1 pp 45ndash49 1995

[61] N Ishihara D-C Chu S Akachi and L R Juneja ldquoImprove-ment of intestinal microflora balance and prevention of diges-tive and respiratory organ diseases in calves by green teaextractsrdquo Livestock Production Science vol 68 no 2-3 pp 217ndash229 2001

[62] P Dolara C Luceri C De Filippo et al ldquoRed wine polyphenolsinfluence carcinogenesis intestinal microflora oxidative dam-age and gene expression profiles of colonicmucosa in F344 ratsrdquoMutation Research-Fundamental and Molecular Mechanisms ofMutagenesis vol 591 no 1-2 pp 237ndash246 2005

[63] S Sembries G Dongowski K Mehrlander F Will and HDietrich ldquoPhysiological effects of extraction juices from applegrape and red beet pomaces in ratsrdquo Journal of Agricultural andFood Chemistry vol 54 no 26 pp 10269ndash10280 2006

[64] S Sembries G Dongowski G Jacobasch K Mehrlander FWill andH Dietrich ldquoEffects of dietary fibre-rich juice colloidsfrom apple pomace extraction juices on intestinal fermentationproducts and microbiota in ratsrdquo British Journal of Nutritionvol 90 no 3 pp 607ndash615 2003

[65] A Viveros S Chamorro M Pizarro I Arija C Centeno andA Brenes ldquoEffects of dietary polyphenol-rich grape productson intestinal microflora and gut morphology in broiler chicksrdquoPoultry Science vol 90 no 3 pp 566ndash578 2011

[66] A H Smith and R I Mackie ldquoEffect of condensed tannins onbacterial diversity andmetabolic activity in the rat gastrointesti-nal tractrdquo Applied and Environmental Microbiology vol 70 no2 pp 1104ndash1115 2004

[67] M Massot-Cladera T Perez-Berezo A Franch M Castelland F J Perez-Cano ldquoCocoa modulatory effect on rat faecalmicrobiota and colonic crosstalkrdquo Archives of Biochemistry andBiophysics vol 527 no 2 pp 105ndash112 2012

[68] M Larrosa M J Yanez-Gascon M V Selma et al ldquoEffectof a low dose of dietary resveratrol on colon microbiotainflammation and tissue damage in a DSS-induced colitis ratmodelrdquo Journal of Agricultural and Food Chemistry vol 57 no6 pp 2211ndash2220 2009

[69] A-L Molan Z Liu andM Kruger ldquoThe ability of blackcurrantextracts to positively modulate key markers of gastrointestinalfunction in ratsrdquoWorld Journal ofMicrobiologyampBiotechnologyvol 26 no 10 pp 1735ndash1743 2010

[70] A Lacombe R W Li D Klimis-Zacas et al ldquoLowbush wildblueberries have the potential to modify gut microbiota andxenobiotic metabolism in the rat colonrdquo PLoS ONE vol 8 no6 Article ID e67497 2013

[71] R Saad M R Rizkallah and R K Aziz ldquoGut Pharmacomicro-biomics the tip of an iceberg of complex interactions betweendrugs and gut-associated microbesrdquo Gut Pathogens vol 4 no1 article 16 2012

[72] E J J Van Velzen J A Westerhuis J P M van Duynhovenet al ldquoMultilevel data analysis of a crossover designed humannutritional intervention studyrdquo Journal of Proteome Researchvol 7 no 10 pp 4483ndash4491 2008

[73] T Okubo N Ishihara H Takahashi et al ldquoEffects of partiallyhydrolyzed guar gum intake on human intestinal microfloraand itsmetabolismrdquoBioscience Biotechnology andBiochemistryvol 58 no 8 pp 1364ndash1369 1994

[74] V Mai H A Katki H Harmsen et al ldquoEffects of a controlleddiet and black tea drinking on the fecalmicroflora compositionand the fecal bile acid profile of human volunteers in a double-blinded ramdomized feeding studyrdquo The Journal of Nutritionvol 134 no 2 pp 473ndash478 2004

[75] J-S Jin M Touyama T Hisada and Y Benno ldquoEffectsof green tea consumption on human fecal microbiota withspecial reference to Bifidobacterium speciesrdquoMicrobiology andImmunology vol 56 no 11 pp 729ndash739 2012

[76] J Yamakoshi S Tokutake M Kikuchi Y Kubota H Konishiand T Mitsuoka ldquoEffect of proantocyanidin -rich extract fromgrape seed on human fecal flora and fecalodorrdquo FASEB Journalvol 15 no 4 p A633 2001

[77] X Tzounis A Rodriguez-Mateos J Vulevic G R Gibson CKwik-Uribe and J P E Spencer ldquoPrebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomizedcontrolled double-blind crossover intervention studyrdquo TheAmerican Journal of Clinical Nutrition vol 93 no 1 pp 62ndash722011

[78] M I Queipo-Ortuno M Boto-Ordonez M Murri et alldquoInfluence of red wine polyphenols and ethanol on the gutmicrobiota ecology and biochemical biomarkersrdquo AmericanJournal of Clinical Nutrition vol 95 no 6 pp 1323ndash1334 2012

[79] K Shinohara Y Ohashi K Kawasumi A Terada and TFujisawa ldquoEffect of apple intake on fecal microbiota andmetabolites in humansrdquo Anaerobe vol 16 no 5 pp 510ndash5152010

[80] C I R Gill G J Mcdougall S Glidewell et al ldquoProfiling ofphenols in human fecal water after raspberry supplementationrdquoJournal of Agricultural and Food Chemistry vol 58 no 19 pp10389ndash10395 2010

[81] S Vendrame S Guglielmetti P Riso S Arioli D Klimis-Zacasand M Porrini ldquoSix-week consumption of a wild blueberry

BioMed Research International 15

powder drink increases Bifidobacteria in the human gutrdquoJournal of Agricultural and Food Chemistry vol 59 no 24 pp12815ndash12820 2011

[82] S Guglielmetti D Fracassetti V Taverniti et al ldquoDifferentialmodulation of human intestinal Bifidobacterium populationsafter consumption of a wild blueberry (Vaccinium angusti-folium) drinkrdquo Journal of Agricultural and Food Chemistry vol61 no 34 pp 8134ndash8140 2013

[83] T Clavel M Fallani P Lepage et al ldquoIsoflavones and func-tional foods alter the dominant intestinal microbiota in post-menopausal womenrdquo Journal of Nutrition vol 135 no 12 pp2786ndash2792 2005

[84] A Costabile A Klinder F Fava et al ldquoWhole-grain wheatbreakfast cereal has a prebiotic effect on the human gut micro-biota a double-blind placebo-controlled crossover studyrdquoBritish Journal of Nutrition vol 99 no 1 pp 110ndash120 2008

[85] A L Carvalho-Wells K Helmolz C Nodet et al ldquoDetermina-tion of the in vivo prebiotic potential of a maize-based wholegrain breakfast cereal a human feeding studyrdquo British Journalof Nutrition vol 104 no 9 pp 1353ndash1356 2010

[86] A Cuervo L Valdes N Salazar et al ldquoPilot study of diet andmicrobiota interactive associations of fibers and polyphenolswith human intestinal bacteriardquo Journal of Agricultural andFood Chemistry vol 62 no 23 pp 5330ndash5336 2014

[87] M Jaquet I Rochat J Moulin C Cavin and R BibilonildquoImpact of coffee consumption on the gut microbiota a humanvolunteer studyrdquo International Journal of FoodMicrobiology vol130 no 2 pp 117ndash121 2009

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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International Journal of

Volume 2014

Zoology

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GenomicsInternational Journal of

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Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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International Journal of

Microbiology

Page 10: Review Article A Survey of Modulation of Gut Microbiota by ...downloads.hindawi.com/journals/bmri/2015/850902.pdf · Review Article A Survey of Modulation of Gut Microbiota by Dietary

10 BioMed Research International

Table4Con

tinued

Reference

Volunteer

number

Phenolic

compo

undfood

Dose

Treatm

ent

duratio

nMicrobial

techniqu

ePo

pulatio

nincrease

Popu

latio

ndecrease

Noeffect

Tzou

nise

tal

(2011)[77]

22Cocoa

flavano

l494m

gday

29mgday

4weeks

FISH

Bifid

obacteriu

mspp

Lactobacillus

spp

Chisto

lyticum

perfringens

grou

p

Vend

ramee

tal(2011)[81]

15Wild

blueberry

drink

25gwild

blueberriesd

ay6weeks

qPCR

Bifid

obacteriu

mspp

Lacidophilus

Bacteroidesspp

Prevotellaspp

Enterococcus

spp

Ccoccoides

Queipo-

Ortun

oetal

(2012)

[78]

10Re

dwine

272m

Lday

20days

qPCR

Enterococcus

spp

Prevotellaspp

Bacteroides

Bifid

obacteriu

mspp

Bacteroidesu

niform

isEggerthella

lenta

Blautia

coccoides-E

rectaleg

roup

Clostridium

spp

Chisto

lyticum

group

Actin

obacteria

Jinetal(2012)

[75]

10Green

tea

1000

mLday

10days

T-RF

LPqP

CRBifid

obacteriu

mspp

Gug

lielm

ettiet

al(2013)[82]

15Wild

blueberries

drink

25gwild

blueberriesd

ay6weeks

qPCR

Blongum

subspinfantis

Cuervo

etal

(2014)

[86]

38

Dairy

prod

ucts

Fruits

Vegetables

Cereals

Food

intake

was

recorded

usingan

annu

alfood

frequ

ency

questio

nnaire

qPCR

Lactobacillus

Bcoccoides

Clep

tum

BioMed Research International 11

three consecutive periods After the red wine period thebacterial concentrations of proteobacteria fusobacteria Fir-micutes and Bacteroidetes markedly increased comparedwith the washout period significant increases in the num-ber of Bifidobacterium spp and Prevotella spp were alsoobserved However Lactobacillus spp Clostridium spp andC histolyticum group concentrations remained unchangedthroughout the study

In a small-scale observational study (119899 = 8) Shinoharaet al [79] found that the number of bifidobacteria in fecessignificantly increased during apple intake and the numbersof Lactobacillus spp Streptococcus spp and Enterococcusspp tended to increase On the contrary enterobacteriaand lecithinase-positive clostridia including C perfringensand Pseudomonas species tended to decrease Howeverthat study did not use culture-independent microbiologytechniques and suffered from the lack of a control groupAlso in relation to fruits another small human interventionstudy (119899 = 10) with raspberry puree [80] did not observestatistically significant alterations in the profile of colonicbacteria probably due to high interindividual variation infecal bacteria although the profiles of microbial metabolitesof raspberry polyphenols varied greatly between individualsindicating that the type of gut microbiota affects cataboliteprofiles released by bacteria in the colonThis lack of effect onthe intestinal microbiota after the intake of raspberry pureemight also be due to the short duration of the treatment aswell as the techniques employed to quantify the intestinalmicrobiota

Vendrame et al [81] studied the potential prebioticactivity of a drink elaborated fromwild blueberries especiallyrich in anthocyanins in a small intervention trial (119899 = 15) Asignificant increase in Bifidobacterium spp and L acidophilusgroup was detected while no significant differences wereobserved for Bacteroides spp Prevotella spp Enterococcusspp and C coccoides In a further paper of the same group[82] seven different intragenus bifidobacteria taxonomicclusters that were among the most common and abundantbifidobacteria species inhabiting the human gutwere targetedin the same samples It was found thatB adolescentisB breveB catenulatumpseudocatenulatum and B longum subsplongumwere always present in the group of subjects enrolledwhereas B bifidum and B longum subsp infantis were notIn spite of the large interindividual variability a significantincrease of B longum subsp infantis cell concentration wasobserved in the feces of volunteers after the wild blueberrydrink treatment which was attributed to the presence ofprebiotic (bifidogenic) molecules from blueberries possiblyfibers and glycosylated anthocyanins

In a study with postmenopausal women (119899 = 39)Clavel et al [83] found that isoflavone supplementationstimulated dominant microorganisms of the C coccoides-Erectale cluster Lactobacillus-Enterococcus group Faecalibac-terium prausnitzii subgroup and Bifidobacterium genus Itwas also suggested that the concentration of C coccoides-Erectale cluster was related to women capacity to excrete equolan intestinal metabolite from daidzein In two interventionstudies with whole grain breakfast cereals from wheat (119899 =31) and maize (119899 = 32) [84 85] the ingestion of both

products resulted in significant increases in fecal bifidobac-teria andor lactobacilli without changing the relative abun-dance of other dominant members of the gut microbiotaLittle or no changes were observed in the numbers of totalbacteria Bacteroides spp C histolyticumperfringens groupand Acetobacterium spp present in the feces However aswhole grains are good sources of dietary fiber it is difficult toascribe the observed effects only to the phenolic compoundspresent in these foods In this respect Cuervo et al [86] haverecently studied the correlations between the intake of fiberand polyphenols from diet and fecal microbiota compositionin a cohort of apparently healthy subjects Results showedthat the intake of soluble pectins and flavanones fromorangespresented a negative correlation with the levels of B coccoidesand C leptum By contrast the intake of white breadproviding hemicellulose and resistant starch was directlycorrelated with Lactobacillus

Finally another human trial (119899 = 16) carried out byJaquet et al [87] assessed the impact of a moderate con-sumption of instant coffee on the general composition ofthe human intestinal bacterial population Coffee bever-ages contain significant amounts of soluble fibre (mainlygalactomannans and arabinogalactan-proteins) and phenoliccompounds (chlorogenic acids) which arewell utilised by thehuman fecal microbiota It was observed that although fecalprofiles of the dominant microbiota were not significantlyaffected after the consumption of the coffee the populationof Bifidobacterium spp increased being the largest increaseobserved for those volunteers showing the lowest initialbifidobacteria levels

8 Conclusions

This review has tried to summarize the current knowledgein relation to the phenolic metabolism by gut microbiota andthemodulation of the gutmicrobiota by phenolic compoundsand polyphenol-rich dietary sourcesThere are evidences thatthe beneficial effects attribute to dietary polyphenols dependon their biotransformation by the gut microbiota Thereforeit is important to investigate the bacterial species impli-cated in the metabolism of dietary polyphenols and furtherresearch is still needed in relation to the resultant microbialmetabolites to ascertain their mechanisms of action Onthe other hand a great number of in vitro and in vivo (inanimals andhumans) studies showing the influence of dietarypolyphenols on gut-inhabiting bacteria have been publishedin recent years Although in vitro assays facilitate experimen-tation caution must be taken in extrapolating results to invivo situation as many factors are acting upon this processIn general in both in vitro and in vivo studies polyphenols orpolyphenol-rich sources have shown to influence the relativeabundance of different bacterial groups within the gut micro-biota reducing numbers of potential pathogens including Cperfringens and C histolyticum and certain Gram-negativeBacteroides spp and enhancing mainly beneficial Clostridiabifidobacteria and lactobacilli A better understanding of theinteraction between dietary polyphenols and gut microbiotathrough the emerging advances in high-throughput meta-genomic transcriptomic and proteomic approaches would

12 BioMed Research International

be essential in order to identify genes and micro-organismsinvolved in polyphenol (in)activation and conversion andthus to elucidate the implications of diet on the modulationof microbiota for delivering health benefits

Functional foods are considered to enhance the protectiveeffects against diseases derived from some food componentsIn the last decades dairy fermented foods have probablybeen one of the most-developed functional products andhave deserved intensive research In this expansion dairyfermented foods have been supplemented with fruits cerealsand other stuffs of plant origin all of which represent a highpercentage of the current market of the dairy industry Theseproducts have a healthy appeal which attracts consumersThus fruit juicesconcentrates and prepared fruits (in theform of pieces pulp and even flour) have been successfullyincorporated in dairy fermented foods as sources of prebioticfibers and phytochemicals Among these phytochemicalspresent in plant-derived foods polyphenols have gainedmuch interest due to their diverse potential beneficial effectsin human health The supplementation of dairy fermentedproducts with rich-polyphenolic stuffs (phenolic extractsphenolic-enriched fractions etc) seems to be an effectivetechnological option to improve the benefits of these productsin the balance of the intestinal microbiota due not only to theaction of the probiotics but also to the potential modulationeffects exerted by polyphenols as it has been described in thisreview Further research in this area will aim to accomplishthe benefits of both probiotic strains and polyphenols inrelation to gut health

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors of this review were funded by the SpanishMINECO through different projects (AGL2012-40172-C02-01 AGL2010-17499 and BFU2012-35228) and the CON-SOLIDER INGENIO 2010 programme (project FUN-C-FOOD CSD2007-063) as well as Comunidad de Madrid(project ALIBIRD P2009AGR-1469) Montserrat Duenaswould like to thank the Spanish ldquoRamon y Cajalrdquo Programmefor a contract

References

[1] S E Power P W OrsquoToole C Stanton R P Ross and GF Fitzgerald ldquoIntestinal microbiota diet and healthrdquo BritishJournal of Nutrition vol 111 no 3 pp 387ndash402 2014

[2] PDeCruz L Prideaux JWagner et al ldquoCharacterization of thegastrointestinal microbiota in health and inflammatory boweldiseaserdquo Inflammatory Bowel Diseases vol 18 no 2 pp 372ndash390 2012

[3] A Kramer S Bekeschus B M Broker H Schleibinger BRazavi and O Assadian ldquoMaintaining health by balancingmicrobial exposure and prevention of infection the hygienehypothesis versus the hypothesis of early immune challengerdquoJournal of Hospital Infection vol 83 no 1 pp S29ndashS34 2013

[4] M Rescigno ldquoIntestinal microbiota and its effects on theimmune systemrdquo Cellular Microbiology vol 16 no 7 pp 1004ndash1013 2014

[5] M G L Hertog E J M Feskens P C H HollmanM B Katanand D Kromhout ldquoDietary antioxidant flavonoids and risk ofcoronary heart disease the Zutphen Elderly StudyrdquoThe Lancetvol 342 no 8878 pp 1007ndash1011 1993

[6] I C W Arts and P C H Hollman ldquoPolyphenols and diseaserisk in epidemiologic studiesrdquoThe American Journal of ClinicalNutrition vol 81 no 1 pp 317Sndash325S 2009

[7] D del Rio A Rodriguez-Mateos J P E Spencer M TognoliniG Borges and A Crozier ldquoDietary (poly)phenolics in humanhealth structures bioavailability and evidence of protectiveeffects against chronic diseasesrdquo Antioxidants amp Redox Signal-ing vol 18 no 14 pp 1818ndash1892 2013

[8] F Perez-Vizcaino and J Duarte ldquoFlavonols and cardiovasculardiseaserdquo Molecular Aspects of Medicine vol 31 no 6 pp 478ndash494 2010

[9] J P E Spencer K Vafeiadou R J Williams and D VauzourldquoNeuroinflammation modulation by flavonoids and mecha-nisms of actionrdquo Molecular Aspects of Medicine vol 33 no 1pp 83ndash97 2012

[10] J M Laparra and Y Sanz ldquoInteractions of gut microbiota withfunctional food components and nutraceuticalsrdquo Pharmacolog-ical Research vol 61 no 3 pp 219ndash225 2010

[11] X He M L Marco and C M Slupsky ldquoEmerging aspects offood and nutrition on gut microbiotardquo Journal of Agriculturaland Food Chemistry vol 61 no 40 pp 9559ndash9574 2013

[12] D Hervert-Hernandez and I Goni ldquoDietary polyphenols andhuman gut microbiota a reviewrdquo Food Reviews Internationalvol 27 no 2 pp 154ndash169 2011

[13] K M Tuohy L Conterno M Gasperotti and R Viola ldquoUp-regulating the human intestinal microbiome using whole plantfoods polyphenols andor fiberrdquo Journal of Agricultural andFood Chemistry vol 60 no 36 pp 8776ndash8782 2012

[14] U Etxeberria A Fernandez-Quintela F I Milagro L AguirreJ A Martınez and M P Portillo ldquoImpact of polyphenols andpolyphenol-rich dietary sources on gut microbiota composi-tionrdquo Journal of Agricultural and Food Chemistry vol 61 no 40pp 9517ndash9533 2013

[15] F Cardona C Andres-Lacueva S Tulipani F J Tinahonesand M I Queipo-Ortuno ldquoBenefits of polyphenols on gutmicrobiota and implications in human healthrdquo Journal ofNutritional Biochemistry vol 24 no 8 pp 1415ndash1422 2013

[16] M V Selma J C Espın and F A Tomas-Barberan ldquoInteractionbetween phenolics and gut microbiota role in human healthrdquoJournal of Agricultural and Food Chemistry vol 57 no 15 pp6485ndash6501 2009

[17] T RequenaMMonagasM A Pozo-Bayon et al ldquoPerspectivesof the potential implications ofwine polyphenols on humanoraland gut microbiotardquo Trends in Food Science amp Technology vol21 no 7 pp 332ndash344 2010

[18] J Van Duynhoven E E Vaughan F van Dorsten et alldquoInteractions of black tea polyphenols with human gut micro-biota implications for gut and cardiovascular health1-4rdquo TheAmerican Journal of Clinical Nutrition vol 98 no 6 pp 1631Sndash1641S 2013

[19] SMoco F-P JMartin and S Rezzi ldquoMetabolomics view on gutmicrobiome modulation by polyphenol-rich foodsrdquo Journal ofProteome Research vol 11 no 10 pp 4781ndash4790 2012

BioMed Research International 13

[20] R K Buddington and P T Sangild ldquoCompanion animalssymposium development of the mammalian gastrointestinaltract the resident microbiota and the role of diet in early liferdquoJournal of Animal Science vol 89 no 5 pp 1506ndash1519 2011

[21] K Tiihonen A C Ouwehand and N Rautonen ldquoHumanintestinal microbiota and healthy ageingrdquo Ageing ResearchReviews vol 9 no 2 pp 107ndash116 2010

[22] D Mariat O Firmesse F Levenez et al ldquoThe firmicutesbacteroidetes ratio of the human microbiota changes with agerdquoBMCMicrobiology vol 9 article 123 2009

[23] M Arumugam J Raes E Pelletier et al ldquoEnterotypes of thehuman gutmicrobiomerdquoNature vol 473 no 7346 pp 174ndash1802011

[24] G D Wu J Chen C Hoffmann et al ldquoLinking long-termdietary patterns with gut microbial enterotypesrdquo Science vol334 no 6052 pp 105ndash108 2011

[25] I B JefferyM J Claesson PWOrsquoToole and F Shanahan ldquoCat-egorization of the gut microbiota enterotypes or gradientsrdquoNature Reviews Microbiology vol 10 no 9 pp 591ndash592 2012

[26] WM de Vos andM Nieuwdorp ldquoGenomics a gut predictionrdquoNature vol 498 no 7452 pp 48ndash49 2013

[27] P B Eckburg E M Bik C N Bernstein et al ldquoMicrobiologydiversity of the human intestinal microbial florardquo Science vol308 no 5728 pp 1635ndash1638 2005

[28] E G Zoetendal C T Collier S Koike R I Mackie and H RGaskins ldquoMolecular ecological analysis of the gastrointestinalmicrobiota a reviewrdquo Journal of Nutrition vol 134 no 2 pp465ndash472 2004

[29] M H Fraher PW OrsquoToole and E MM Quigley ldquoTechniquesused to characterize the gut microbiota a guide for the clini-cianrdquo Nature Reviews Gastroenterology and Hepatology vol 9no 6 pp 312ndash322 2012

[30] R A Kemperman S Bolca L C Roger and E E VaughanldquoNovel approaches for analysing gut microbes and dietarypolyphenols challenges and opportunitiesrdquo Microbiology vol156 no 11 pp 3224ndash3231 2010

[31] R A Kemperman G Gross S Mondot et al ldquoImpact ofpolyphenols from black tea and red winegrape juice on a gutmodel microbiomerdquo Food Research International vol 53 no 2pp 659ndash669 2013

[32] M N Clifford ldquoDiet-derived phenols in plasma and tissues andtheir implications for healthrdquo Planta Medica vol 70 no 12 pp1103ndash1114 2004

[33] A Crozier D del Rio and M N Clifford ldquoBioavailability ofdietary flavonoids and phenolic compoundsrdquoMolecular Aspectsof Medicine vol 31 no 6 pp 446ndash467 2010

[34] A J Day M S Dupont S Ridley et al ldquoDeglycosylation offlavonoid and isoflavonoid glycosides by human small intestineand liver beta-glucosidase activityrdquo FEBS Letters vol 436 no 1pp 71ndash75 1998

[35] A J Day F J Canada J C Dıaz et al ldquoDietary flavonoid andisoflavone glycosides are hydrolysed by the lactase site of lactasephlorizin hydrolaserdquo FEBS Letters vol 468 no 2-3 pp 166ndash1702000

[36] A Scalbert and G Williamson ldquoDietary intake and bioavail-ability of polyphenolsrdquo Journal of Nutrition vol 130 no 8 pp2073Sndash2085S 2000

[37] A R Rechner G Kuhnle H Hu et al ldquoThe metabolism ofdietary polyphenols and the relevance to circulating levels ofconjugated metabolitesrdquo Free Radical Research vol 36 no 11pp 1229ndash1241 2002

[38] A-M Aura K A OrsquoLeary G Williamson et al ldquoQuercetinderivatives are deconjugated and converted to hydroxypheny-lacetic acids but not methylated by human fecal flora in vitrordquoJournal of Agricultural and Food Chemistry vol 50 no 6 pp1725ndash1730 2002

[39] A-M Aura ldquoMicrobial metabolism of dietary phenolic com-pounds in the colonrdquo Phytochemistry Reviews vol 7 no 3 pp407ndash429 2008

[40] M Monagas M Urpi-Sarda F Sanchez-Patan et al ldquoInsightsinto themetabolism andmicrobial biotransformation of dietaryflavan-3-ols and the bioactivity of their metabolitesrdquo Food andFunction vol 1 no 3 pp 233ndash253 2010

[41] GWilliamson andMNClifford ldquoColonicmetabolites of berrypolyphenols the missing link to biological activityrdquo BritishJournal of Nutrition vol 104 no 3 pp S48ndashS66 2010

[42] D M Jacobs E Gaudier J van Duynhoven and E E VaughanldquoNon-digestible food ingredients colonic microbiota and theimpact on gut health and immunity a role for metabolomicsrdquoCurrent Drug Metabolism vol 10 no 1 pp 41ndash54 2009

[43] S Bolca S Possemiers V Maervoet et al ldquoMicrobial anddietary factors associatedwith the 8-prenylnaringenin producerphenotype a dietary intervention trial with fifty healthy post-menopausal Caucasian womenrdquo British Journal of Nutritionvol 98 no 5 pp 950ndash959 2007

[44] X Tzounis J Vulevic G G C Kuhnle et al ldquoFlavanolmonomer-induced changes to the human faecal microflorardquoBritish Journal of Nutrition vol 99 no 4 pp 782ndash792 2008

[45] M Hidalgo M J Oruna-Concha S Kolida et al ldquoMetabolismof anthocyanins by human gut microflora and their influenceon gut bacterial growthrdquo Journal of Agricultural and FoodChemistry vol 60 no 15 pp 3882ndash3890 2012

[46] A L Molan M A Lila J Mawson and S De ldquoIn vitroand in vivo evaluation of the prebiotic activity of water-soluble blueberry extractsrdquo World Journal of Microbiology andBiotechnology vol 25 no 7 pp 1243ndash1249 2009

[47] D Bialonska P Ramnani S G Kasimsetty K R Muntha GR Gibson and D Ferreira ldquoThe influence of pomegranate by-product and punicalagins on selected groups of human intesti-nal microbiotardquo International Journal of FoodMicrobiology vol140 no 2-3 pp 175ndash182 2010

[48] G Mandalari R M Faulks C Bisignano K W Waldron ANarbad and M S J Wickham ldquoIn vitro evaluation of theprebiotic properties of almond skins (Amygdalus communisL)rdquoFEMS Microbiology Letters vol 304 no 2 pp 116ndash122 2010

[49] V Fogliano M L Corollaro P Vitaglione et al ldquoIn vitro bioac-cessibility and gut biotransformation of polyphenols present inthe water-insoluble cocoa fractionrdquoMolecular Nutritionamp FoodResearch vol 55 supplement 1 pp S44ndashS55 2011

[50] M J Pozuelo A Agis-Torres D Hervert-Hernandez etal ldquoGrape antioxidant dietary fiber stimulates Lactobacillusgrowth in rat cecumrdquo Journal of Food Science vol 77 no 2 ppH59ndashH62 2012

[51] C Cueva F Sanchez-Patan M Monagas et al ldquoIn vitrofermentation of grape seed flavan-3-ol fractions by humanfaecal microbiota changes in microbial groups and phenolicmetabolitesrdquo FEMSMicrobiology Ecology vol 83 no 3 pp 792ndash805 2013

[52] F Sanchez-Patan C CuevaMMonagas et al ldquoIn vitro fermen-tation of a red wine extract by human gut microbiota changesin microbial groups and formation of phenolic metabolitesrdquoJournal of Agricultural and Food Chemistry vol 60 no 9 pp2136ndash2147 2012

14 BioMed Research International

[53] E Barroso F Sanchez-Patan P J Martın-Alvarez et al ldquoLacto-bacillus plantarum IFPL935 favors the initial metabolism of redwine polyphenols when added to a colonic microbiotardquo Journalof Agricultural and Food Chemistry vol 61 no 42 pp 10163ndash10172 2013

[54] G R Gibson J H Cummings and G T Macfarlane ldquoUse ofa three-stage continuous culture system to study the effect ofmucin on dissimilatory sulfate reduction and methanogenesisby mixed populations of human gut bacteriardquo Applied andEnvironmentalMicrobiology vol 54 no 11 pp 2750ndash2755 1988

[55] KMollyMVandeWoestyne andWVerstraete ldquoDevelopmentof a 5-step multi-chamber reactor as a simulation of thehuman intestinal microbial ecosystemrdquo Applied Microbiologyand Biotechnology vol 39 no 2 pp 254ndash258 1993

[56] M Minekus M Smeets-Peeters A Bernalier et al ldquoAcomputer-controlled system to simulate conditions of thelarge intestine with peristaltic mixing water absorption andabsorption of fermentation productsrdquoAppliedMicrobiology andBiotechnology vol 53 no 1 pp 108ndash114 1999

[57] PDeBoever BDeplancke andWVerstraete ldquoFermentation bygut microbiota cultured in a simulator of the human intestinalmicrobial ecosystem is improved by supplementing a soygermpowderrdquo Journal of Nutrition vol 130 no 10 pp 2599ndash26062000

[58] C S Yang X Wang G Lu and S C Picinich ldquoCancerprevention by tea animal studies molecular mechanisms andhuman relevancerdquoNature Reviews Cancer vol 9 no 6 pp 429ndash439 2009

[59] R E Ley F Backhed P Turnbaugh C A Lozupone R DKnight and J I Gordon ldquoObesity alters gut microbial ecologyrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 102 no 31 pp 11070ndash11075 2005

[60] H Hara N Orita S Hatano et al ldquoEffect of tea polyphenols onfecal flora and fecal metabolic products of pigsrdquo The Journal ofVeterinary Medical Science vol 57 no 1 pp 45ndash49 1995

[61] N Ishihara D-C Chu S Akachi and L R Juneja ldquoImprove-ment of intestinal microflora balance and prevention of diges-tive and respiratory organ diseases in calves by green teaextractsrdquo Livestock Production Science vol 68 no 2-3 pp 217ndash229 2001

[62] P Dolara C Luceri C De Filippo et al ldquoRed wine polyphenolsinfluence carcinogenesis intestinal microflora oxidative dam-age and gene expression profiles of colonicmucosa in F344 ratsrdquoMutation Research-Fundamental and Molecular Mechanisms ofMutagenesis vol 591 no 1-2 pp 237ndash246 2005

[63] S Sembries G Dongowski K Mehrlander F Will and HDietrich ldquoPhysiological effects of extraction juices from applegrape and red beet pomaces in ratsrdquo Journal of Agricultural andFood Chemistry vol 54 no 26 pp 10269ndash10280 2006

[64] S Sembries G Dongowski G Jacobasch K Mehrlander FWill andH Dietrich ldquoEffects of dietary fibre-rich juice colloidsfrom apple pomace extraction juices on intestinal fermentationproducts and microbiota in ratsrdquo British Journal of Nutritionvol 90 no 3 pp 607ndash615 2003

[65] A Viveros S Chamorro M Pizarro I Arija C Centeno andA Brenes ldquoEffects of dietary polyphenol-rich grape productson intestinal microflora and gut morphology in broiler chicksrdquoPoultry Science vol 90 no 3 pp 566ndash578 2011

[66] A H Smith and R I Mackie ldquoEffect of condensed tannins onbacterial diversity andmetabolic activity in the rat gastrointesti-nal tractrdquo Applied and Environmental Microbiology vol 70 no2 pp 1104ndash1115 2004

[67] M Massot-Cladera T Perez-Berezo A Franch M Castelland F J Perez-Cano ldquoCocoa modulatory effect on rat faecalmicrobiota and colonic crosstalkrdquo Archives of Biochemistry andBiophysics vol 527 no 2 pp 105ndash112 2012

[68] M Larrosa M J Yanez-Gascon M V Selma et al ldquoEffectof a low dose of dietary resveratrol on colon microbiotainflammation and tissue damage in a DSS-induced colitis ratmodelrdquo Journal of Agricultural and Food Chemistry vol 57 no6 pp 2211ndash2220 2009

[69] A-L Molan Z Liu andM Kruger ldquoThe ability of blackcurrantextracts to positively modulate key markers of gastrointestinalfunction in ratsrdquoWorld Journal ofMicrobiologyampBiotechnologyvol 26 no 10 pp 1735ndash1743 2010

[70] A Lacombe R W Li D Klimis-Zacas et al ldquoLowbush wildblueberries have the potential to modify gut microbiota andxenobiotic metabolism in the rat colonrdquo PLoS ONE vol 8 no6 Article ID e67497 2013

[71] R Saad M R Rizkallah and R K Aziz ldquoGut Pharmacomicro-biomics the tip of an iceberg of complex interactions betweendrugs and gut-associated microbesrdquo Gut Pathogens vol 4 no1 article 16 2012

[72] E J J Van Velzen J A Westerhuis J P M van Duynhovenet al ldquoMultilevel data analysis of a crossover designed humannutritional intervention studyrdquo Journal of Proteome Researchvol 7 no 10 pp 4483ndash4491 2008

[73] T Okubo N Ishihara H Takahashi et al ldquoEffects of partiallyhydrolyzed guar gum intake on human intestinal microfloraand itsmetabolismrdquoBioscience Biotechnology andBiochemistryvol 58 no 8 pp 1364ndash1369 1994

[74] V Mai H A Katki H Harmsen et al ldquoEffects of a controlleddiet and black tea drinking on the fecalmicroflora compositionand the fecal bile acid profile of human volunteers in a double-blinded ramdomized feeding studyrdquo The Journal of Nutritionvol 134 no 2 pp 473ndash478 2004

[75] J-S Jin M Touyama T Hisada and Y Benno ldquoEffectsof green tea consumption on human fecal microbiota withspecial reference to Bifidobacterium speciesrdquoMicrobiology andImmunology vol 56 no 11 pp 729ndash739 2012

[76] J Yamakoshi S Tokutake M Kikuchi Y Kubota H Konishiand T Mitsuoka ldquoEffect of proantocyanidin -rich extract fromgrape seed on human fecal flora and fecalodorrdquo FASEB Journalvol 15 no 4 p A633 2001

[77] X Tzounis A Rodriguez-Mateos J Vulevic G R Gibson CKwik-Uribe and J P E Spencer ldquoPrebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomizedcontrolled double-blind crossover intervention studyrdquo TheAmerican Journal of Clinical Nutrition vol 93 no 1 pp 62ndash722011

[78] M I Queipo-Ortuno M Boto-Ordonez M Murri et alldquoInfluence of red wine polyphenols and ethanol on the gutmicrobiota ecology and biochemical biomarkersrdquo AmericanJournal of Clinical Nutrition vol 95 no 6 pp 1323ndash1334 2012

[79] K Shinohara Y Ohashi K Kawasumi A Terada and TFujisawa ldquoEffect of apple intake on fecal microbiota andmetabolites in humansrdquo Anaerobe vol 16 no 5 pp 510ndash5152010

[80] C I R Gill G J Mcdougall S Glidewell et al ldquoProfiling ofphenols in human fecal water after raspberry supplementationrdquoJournal of Agricultural and Food Chemistry vol 58 no 19 pp10389ndash10395 2010

[81] S Vendrame S Guglielmetti P Riso S Arioli D Klimis-Zacasand M Porrini ldquoSix-week consumption of a wild blueberry

BioMed Research International 15

powder drink increases Bifidobacteria in the human gutrdquoJournal of Agricultural and Food Chemistry vol 59 no 24 pp12815ndash12820 2011

[82] S Guglielmetti D Fracassetti V Taverniti et al ldquoDifferentialmodulation of human intestinal Bifidobacterium populationsafter consumption of a wild blueberry (Vaccinium angusti-folium) drinkrdquo Journal of Agricultural and Food Chemistry vol61 no 34 pp 8134ndash8140 2013

[83] T Clavel M Fallani P Lepage et al ldquoIsoflavones and func-tional foods alter the dominant intestinal microbiota in post-menopausal womenrdquo Journal of Nutrition vol 135 no 12 pp2786ndash2792 2005

[84] A Costabile A Klinder F Fava et al ldquoWhole-grain wheatbreakfast cereal has a prebiotic effect on the human gut micro-biota a double-blind placebo-controlled crossover studyrdquoBritish Journal of Nutrition vol 99 no 1 pp 110ndash120 2008

[85] A L Carvalho-Wells K Helmolz C Nodet et al ldquoDetermina-tion of the in vivo prebiotic potential of a maize-based wholegrain breakfast cereal a human feeding studyrdquo British Journalof Nutrition vol 104 no 9 pp 1353ndash1356 2010

[86] A Cuervo L Valdes N Salazar et al ldquoPilot study of diet andmicrobiota interactive associations of fibers and polyphenolswith human intestinal bacteriardquo Journal of Agricultural andFood Chemistry vol 62 no 23 pp 5330ndash5336 2014

[87] M Jaquet I Rochat J Moulin C Cavin and R BibilonildquoImpact of coffee consumption on the gut microbiota a humanvolunteer studyrdquo International Journal of FoodMicrobiology vol130 no 2 pp 117ndash121 2009

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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International Journal of

Microbiology

Page 11: Review Article A Survey of Modulation of Gut Microbiota by ...downloads.hindawi.com/journals/bmri/2015/850902.pdf · Review Article A Survey of Modulation of Gut Microbiota by Dietary

BioMed Research International 11

three consecutive periods After the red wine period thebacterial concentrations of proteobacteria fusobacteria Fir-micutes and Bacteroidetes markedly increased comparedwith the washout period significant increases in the num-ber of Bifidobacterium spp and Prevotella spp were alsoobserved However Lactobacillus spp Clostridium spp andC histolyticum group concentrations remained unchangedthroughout the study

In a small-scale observational study (119899 = 8) Shinoharaet al [79] found that the number of bifidobacteria in fecessignificantly increased during apple intake and the numbersof Lactobacillus spp Streptococcus spp and Enterococcusspp tended to increase On the contrary enterobacteriaand lecithinase-positive clostridia including C perfringensand Pseudomonas species tended to decrease Howeverthat study did not use culture-independent microbiologytechniques and suffered from the lack of a control groupAlso in relation to fruits another small human interventionstudy (119899 = 10) with raspberry puree [80] did not observestatistically significant alterations in the profile of colonicbacteria probably due to high interindividual variation infecal bacteria although the profiles of microbial metabolitesof raspberry polyphenols varied greatly between individualsindicating that the type of gut microbiota affects cataboliteprofiles released by bacteria in the colonThis lack of effect onthe intestinal microbiota after the intake of raspberry pureemight also be due to the short duration of the treatment aswell as the techniques employed to quantify the intestinalmicrobiota

Vendrame et al [81] studied the potential prebioticactivity of a drink elaborated fromwild blueberries especiallyrich in anthocyanins in a small intervention trial (119899 = 15) Asignificant increase in Bifidobacterium spp and L acidophilusgroup was detected while no significant differences wereobserved for Bacteroides spp Prevotella spp Enterococcusspp and C coccoides In a further paper of the same group[82] seven different intragenus bifidobacteria taxonomicclusters that were among the most common and abundantbifidobacteria species inhabiting the human gutwere targetedin the same samples It was found thatB adolescentisB breveB catenulatumpseudocatenulatum and B longum subsplongumwere always present in the group of subjects enrolledwhereas B bifidum and B longum subsp infantis were notIn spite of the large interindividual variability a significantincrease of B longum subsp infantis cell concentration wasobserved in the feces of volunteers after the wild blueberrydrink treatment which was attributed to the presence ofprebiotic (bifidogenic) molecules from blueberries possiblyfibers and glycosylated anthocyanins

In a study with postmenopausal women (119899 = 39)Clavel et al [83] found that isoflavone supplementationstimulated dominant microorganisms of the C coccoides-Erectale cluster Lactobacillus-Enterococcus group Faecalibac-terium prausnitzii subgroup and Bifidobacterium genus Itwas also suggested that the concentration of C coccoides-Erectale cluster was related to women capacity to excrete equolan intestinal metabolite from daidzein In two interventionstudies with whole grain breakfast cereals from wheat (119899 =31) and maize (119899 = 32) [84 85] the ingestion of both

products resulted in significant increases in fecal bifidobac-teria andor lactobacilli without changing the relative abun-dance of other dominant members of the gut microbiotaLittle or no changes were observed in the numbers of totalbacteria Bacteroides spp C histolyticumperfringens groupand Acetobacterium spp present in the feces However aswhole grains are good sources of dietary fiber it is difficult toascribe the observed effects only to the phenolic compoundspresent in these foods In this respect Cuervo et al [86] haverecently studied the correlations between the intake of fiberand polyphenols from diet and fecal microbiota compositionin a cohort of apparently healthy subjects Results showedthat the intake of soluble pectins and flavanones fromorangespresented a negative correlation with the levels of B coccoidesand C leptum By contrast the intake of white breadproviding hemicellulose and resistant starch was directlycorrelated with Lactobacillus

Finally another human trial (119899 = 16) carried out byJaquet et al [87] assessed the impact of a moderate con-sumption of instant coffee on the general composition ofthe human intestinal bacterial population Coffee bever-ages contain significant amounts of soluble fibre (mainlygalactomannans and arabinogalactan-proteins) and phenoliccompounds (chlorogenic acids) which arewell utilised by thehuman fecal microbiota It was observed that although fecalprofiles of the dominant microbiota were not significantlyaffected after the consumption of the coffee the populationof Bifidobacterium spp increased being the largest increaseobserved for those volunteers showing the lowest initialbifidobacteria levels

8 Conclusions

This review has tried to summarize the current knowledgein relation to the phenolic metabolism by gut microbiota andthemodulation of the gutmicrobiota by phenolic compoundsand polyphenol-rich dietary sourcesThere are evidences thatthe beneficial effects attribute to dietary polyphenols dependon their biotransformation by the gut microbiota Thereforeit is important to investigate the bacterial species impli-cated in the metabolism of dietary polyphenols and furtherresearch is still needed in relation to the resultant microbialmetabolites to ascertain their mechanisms of action Onthe other hand a great number of in vitro and in vivo (inanimals andhumans) studies showing the influence of dietarypolyphenols on gut-inhabiting bacteria have been publishedin recent years Although in vitro assays facilitate experimen-tation caution must be taken in extrapolating results to invivo situation as many factors are acting upon this processIn general in both in vitro and in vivo studies polyphenols orpolyphenol-rich sources have shown to influence the relativeabundance of different bacterial groups within the gut micro-biota reducing numbers of potential pathogens including Cperfringens and C histolyticum and certain Gram-negativeBacteroides spp and enhancing mainly beneficial Clostridiabifidobacteria and lactobacilli A better understanding of theinteraction between dietary polyphenols and gut microbiotathrough the emerging advances in high-throughput meta-genomic transcriptomic and proteomic approaches would

12 BioMed Research International

be essential in order to identify genes and micro-organismsinvolved in polyphenol (in)activation and conversion andthus to elucidate the implications of diet on the modulationof microbiota for delivering health benefits

Functional foods are considered to enhance the protectiveeffects against diseases derived from some food componentsIn the last decades dairy fermented foods have probablybeen one of the most-developed functional products andhave deserved intensive research In this expansion dairyfermented foods have been supplemented with fruits cerealsand other stuffs of plant origin all of which represent a highpercentage of the current market of the dairy industry Theseproducts have a healthy appeal which attracts consumersThus fruit juicesconcentrates and prepared fruits (in theform of pieces pulp and even flour) have been successfullyincorporated in dairy fermented foods as sources of prebioticfibers and phytochemicals Among these phytochemicalspresent in plant-derived foods polyphenols have gainedmuch interest due to their diverse potential beneficial effectsin human health The supplementation of dairy fermentedproducts with rich-polyphenolic stuffs (phenolic extractsphenolic-enriched fractions etc) seems to be an effectivetechnological option to improve the benefits of these productsin the balance of the intestinal microbiota due not only to theaction of the probiotics but also to the potential modulationeffects exerted by polyphenols as it has been described in thisreview Further research in this area will aim to accomplishthe benefits of both probiotic strains and polyphenols inrelation to gut health

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors of this review were funded by the SpanishMINECO through different projects (AGL2012-40172-C02-01 AGL2010-17499 and BFU2012-35228) and the CON-SOLIDER INGENIO 2010 programme (project FUN-C-FOOD CSD2007-063) as well as Comunidad de Madrid(project ALIBIRD P2009AGR-1469) Montserrat Duenaswould like to thank the Spanish ldquoRamon y Cajalrdquo Programmefor a contract

References

[1] S E Power P W OrsquoToole C Stanton R P Ross and GF Fitzgerald ldquoIntestinal microbiota diet and healthrdquo BritishJournal of Nutrition vol 111 no 3 pp 387ndash402 2014

[2] PDeCruz L Prideaux JWagner et al ldquoCharacterization of thegastrointestinal microbiota in health and inflammatory boweldiseaserdquo Inflammatory Bowel Diseases vol 18 no 2 pp 372ndash390 2012

[3] A Kramer S Bekeschus B M Broker H Schleibinger BRazavi and O Assadian ldquoMaintaining health by balancingmicrobial exposure and prevention of infection the hygienehypothesis versus the hypothesis of early immune challengerdquoJournal of Hospital Infection vol 83 no 1 pp S29ndashS34 2013

[4] M Rescigno ldquoIntestinal microbiota and its effects on theimmune systemrdquo Cellular Microbiology vol 16 no 7 pp 1004ndash1013 2014

[5] M G L Hertog E J M Feskens P C H HollmanM B Katanand D Kromhout ldquoDietary antioxidant flavonoids and risk ofcoronary heart disease the Zutphen Elderly StudyrdquoThe Lancetvol 342 no 8878 pp 1007ndash1011 1993

[6] I C W Arts and P C H Hollman ldquoPolyphenols and diseaserisk in epidemiologic studiesrdquoThe American Journal of ClinicalNutrition vol 81 no 1 pp 317Sndash325S 2009

[7] D del Rio A Rodriguez-Mateos J P E Spencer M TognoliniG Borges and A Crozier ldquoDietary (poly)phenolics in humanhealth structures bioavailability and evidence of protectiveeffects against chronic diseasesrdquo Antioxidants amp Redox Signal-ing vol 18 no 14 pp 1818ndash1892 2013

[8] F Perez-Vizcaino and J Duarte ldquoFlavonols and cardiovasculardiseaserdquo Molecular Aspects of Medicine vol 31 no 6 pp 478ndash494 2010

[9] J P E Spencer K Vafeiadou R J Williams and D VauzourldquoNeuroinflammation modulation by flavonoids and mecha-nisms of actionrdquo Molecular Aspects of Medicine vol 33 no 1pp 83ndash97 2012

[10] J M Laparra and Y Sanz ldquoInteractions of gut microbiota withfunctional food components and nutraceuticalsrdquo Pharmacolog-ical Research vol 61 no 3 pp 219ndash225 2010

[11] X He M L Marco and C M Slupsky ldquoEmerging aspects offood and nutrition on gut microbiotardquo Journal of Agriculturaland Food Chemistry vol 61 no 40 pp 9559ndash9574 2013

[12] D Hervert-Hernandez and I Goni ldquoDietary polyphenols andhuman gut microbiota a reviewrdquo Food Reviews Internationalvol 27 no 2 pp 154ndash169 2011

[13] K M Tuohy L Conterno M Gasperotti and R Viola ldquoUp-regulating the human intestinal microbiome using whole plantfoods polyphenols andor fiberrdquo Journal of Agricultural andFood Chemistry vol 60 no 36 pp 8776ndash8782 2012

[14] U Etxeberria A Fernandez-Quintela F I Milagro L AguirreJ A Martınez and M P Portillo ldquoImpact of polyphenols andpolyphenol-rich dietary sources on gut microbiota composi-tionrdquo Journal of Agricultural and Food Chemistry vol 61 no 40pp 9517ndash9533 2013

[15] F Cardona C Andres-Lacueva S Tulipani F J Tinahonesand M I Queipo-Ortuno ldquoBenefits of polyphenols on gutmicrobiota and implications in human healthrdquo Journal ofNutritional Biochemistry vol 24 no 8 pp 1415ndash1422 2013

[16] M V Selma J C Espın and F A Tomas-Barberan ldquoInteractionbetween phenolics and gut microbiota role in human healthrdquoJournal of Agricultural and Food Chemistry vol 57 no 15 pp6485ndash6501 2009

[17] T RequenaMMonagasM A Pozo-Bayon et al ldquoPerspectivesof the potential implications ofwine polyphenols on humanoraland gut microbiotardquo Trends in Food Science amp Technology vol21 no 7 pp 332ndash344 2010

[18] J Van Duynhoven E E Vaughan F van Dorsten et alldquoInteractions of black tea polyphenols with human gut micro-biota implications for gut and cardiovascular health1-4rdquo TheAmerican Journal of Clinical Nutrition vol 98 no 6 pp 1631Sndash1641S 2013

[19] SMoco F-P JMartin and S Rezzi ldquoMetabolomics view on gutmicrobiome modulation by polyphenol-rich foodsrdquo Journal ofProteome Research vol 11 no 10 pp 4781ndash4790 2012

BioMed Research International 13

[20] R K Buddington and P T Sangild ldquoCompanion animalssymposium development of the mammalian gastrointestinaltract the resident microbiota and the role of diet in early liferdquoJournal of Animal Science vol 89 no 5 pp 1506ndash1519 2011

[21] K Tiihonen A C Ouwehand and N Rautonen ldquoHumanintestinal microbiota and healthy ageingrdquo Ageing ResearchReviews vol 9 no 2 pp 107ndash116 2010

[22] D Mariat O Firmesse F Levenez et al ldquoThe firmicutesbacteroidetes ratio of the human microbiota changes with agerdquoBMCMicrobiology vol 9 article 123 2009

[23] M Arumugam J Raes E Pelletier et al ldquoEnterotypes of thehuman gutmicrobiomerdquoNature vol 473 no 7346 pp 174ndash1802011

[24] G D Wu J Chen C Hoffmann et al ldquoLinking long-termdietary patterns with gut microbial enterotypesrdquo Science vol334 no 6052 pp 105ndash108 2011

[25] I B JefferyM J Claesson PWOrsquoToole and F Shanahan ldquoCat-egorization of the gut microbiota enterotypes or gradientsrdquoNature Reviews Microbiology vol 10 no 9 pp 591ndash592 2012

[26] WM de Vos andM Nieuwdorp ldquoGenomics a gut predictionrdquoNature vol 498 no 7452 pp 48ndash49 2013

[27] P B Eckburg E M Bik C N Bernstein et al ldquoMicrobiologydiversity of the human intestinal microbial florardquo Science vol308 no 5728 pp 1635ndash1638 2005

[28] E G Zoetendal C T Collier S Koike R I Mackie and H RGaskins ldquoMolecular ecological analysis of the gastrointestinalmicrobiota a reviewrdquo Journal of Nutrition vol 134 no 2 pp465ndash472 2004

[29] M H Fraher PW OrsquoToole and E MM Quigley ldquoTechniquesused to characterize the gut microbiota a guide for the clini-cianrdquo Nature Reviews Gastroenterology and Hepatology vol 9no 6 pp 312ndash322 2012

[30] R A Kemperman S Bolca L C Roger and E E VaughanldquoNovel approaches for analysing gut microbes and dietarypolyphenols challenges and opportunitiesrdquo Microbiology vol156 no 11 pp 3224ndash3231 2010

[31] R A Kemperman G Gross S Mondot et al ldquoImpact ofpolyphenols from black tea and red winegrape juice on a gutmodel microbiomerdquo Food Research International vol 53 no 2pp 659ndash669 2013

[32] M N Clifford ldquoDiet-derived phenols in plasma and tissues andtheir implications for healthrdquo Planta Medica vol 70 no 12 pp1103ndash1114 2004

[33] A Crozier D del Rio and M N Clifford ldquoBioavailability ofdietary flavonoids and phenolic compoundsrdquoMolecular Aspectsof Medicine vol 31 no 6 pp 446ndash467 2010

[34] A J Day M S Dupont S Ridley et al ldquoDeglycosylation offlavonoid and isoflavonoid glycosides by human small intestineand liver beta-glucosidase activityrdquo FEBS Letters vol 436 no 1pp 71ndash75 1998

[35] A J Day F J Canada J C Dıaz et al ldquoDietary flavonoid andisoflavone glycosides are hydrolysed by the lactase site of lactasephlorizin hydrolaserdquo FEBS Letters vol 468 no 2-3 pp 166ndash1702000

[36] A Scalbert and G Williamson ldquoDietary intake and bioavail-ability of polyphenolsrdquo Journal of Nutrition vol 130 no 8 pp2073Sndash2085S 2000

[37] A R Rechner G Kuhnle H Hu et al ldquoThe metabolism ofdietary polyphenols and the relevance to circulating levels ofconjugated metabolitesrdquo Free Radical Research vol 36 no 11pp 1229ndash1241 2002

[38] A-M Aura K A OrsquoLeary G Williamson et al ldquoQuercetinderivatives are deconjugated and converted to hydroxypheny-lacetic acids but not methylated by human fecal flora in vitrordquoJournal of Agricultural and Food Chemistry vol 50 no 6 pp1725ndash1730 2002

[39] A-M Aura ldquoMicrobial metabolism of dietary phenolic com-pounds in the colonrdquo Phytochemistry Reviews vol 7 no 3 pp407ndash429 2008

[40] M Monagas M Urpi-Sarda F Sanchez-Patan et al ldquoInsightsinto themetabolism andmicrobial biotransformation of dietaryflavan-3-ols and the bioactivity of their metabolitesrdquo Food andFunction vol 1 no 3 pp 233ndash253 2010

[41] GWilliamson andMNClifford ldquoColonicmetabolites of berrypolyphenols the missing link to biological activityrdquo BritishJournal of Nutrition vol 104 no 3 pp S48ndashS66 2010

[42] D M Jacobs E Gaudier J van Duynhoven and E E VaughanldquoNon-digestible food ingredients colonic microbiota and theimpact on gut health and immunity a role for metabolomicsrdquoCurrent Drug Metabolism vol 10 no 1 pp 41ndash54 2009

[43] S Bolca S Possemiers V Maervoet et al ldquoMicrobial anddietary factors associatedwith the 8-prenylnaringenin producerphenotype a dietary intervention trial with fifty healthy post-menopausal Caucasian womenrdquo British Journal of Nutritionvol 98 no 5 pp 950ndash959 2007

[44] X Tzounis J Vulevic G G C Kuhnle et al ldquoFlavanolmonomer-induced changes to the human faecal microflorardquoBritish Journal of Nutrition vol 99 no 4 pp 782ndash792 2008

[45] M Hidalgo M J Oruna-Concha S Kolida et al ldquoMetabolismof anthocyanins by human gut microflora and their influenceon gut bacterial growthrdquo Journal of Agricultural and FoodChemistry vol 60 no 15 pp 3882ndash3890 2012

[46] A L Molan M A Lila J Mawson and S De ldquoIn vitroand in vivo evaluation of the prebiotic activity of water-soluble blueberry extractsrdquo World Journal of Microbiology andBiotechnology vol 25 no 7 pp 1243ndash1249 2009

[47] D Bialonska P Ramnani S G Kasimsetty K R Muntha GR Gibson and D Ferreira ldquoThe influence of pomegranate by-product and punicalagins on selected groups of human intesti-nal microbiotardquo International Journal of FoodMicrobiology vol140 no 2-3 pp 175ndash182 2010

[48] G Mandalari R M Faulks C Bisignano K W Waldron ANarbad and M S J Wickham ldquoIn vitro evaluation of theprebiotic properties of almond skins (Amygdalus communisL)rdquoFEMS Microbiology Letters vol 304 no 2 pp 116ndash122 2010

[49] V Fogliano M L Corollaro P Vitaglione et al ldquoIn vitro bioac-cessibility and gut biotransformation of polyphenols present inthe water-insoluble cocoa fractionrdquoMolecular Nutritionamp FoodResearch vol 55 supplement 1 pp S44ndashS55 2011

[50] M J Pozuelo A Agis-Torres D Hervert-Hernandez etal ldquoGrape antioxidant dietary fiber stimulates Lactobacillusgrowth in rat cecumrdquo Journal of Food Science vol 77 no 2 ppH59ndashH62 2012

[51] C Cueva F Sanchez-Patan M Monagas et al ldquoIn vitrofermentation of grape seed flavan-3-ol fractions by humanfaecal microbiota changes in microbial groups and phenolicmetabolitesrdquo FEMSMicrobiology Ecology vol 83 no 3 pp 792ndash805 2013

[52] F Sanchez-Patan C CuevaMMonagas et al ldquoIn vitro fermen-tation of a red wine extract by human gut microbiota changesin microbial groups and formation of phenolic metabolitesrdquoJournal of Agricultural and Food Chemistry vol 60 no 9 pp2136ndash2147 2012

14 BioMed Research International

[53] E Barroso F Sanchez-Patan P J Martın-Alvarez et al ldquoLacto-bacillus plantarum IFPL935 favors the initial metabolism of redwine polyphenols when added to a colonic microbiotardquo Journalof Agricultural and Food Chemistry vol 61 no 42 pp 10163ndash10172 2013

[54] G R Gibson J H Cummings and G T Macfarlane ldquoUse ofa three-stage continuous culture system to study the effect ofmucin on dissimilatory sulfate reduction and methanogenesisby mixed populations of human gut bacteriardquo Applied andEnvironmentalMicrobiology vol 54 no 11 pp 2750ndash2755 1988

[55] KMollyMVandeWoestyne andWVerstraete ldquoDevelopmentof a 5-step multi-chamber reactor as a simulation of thehuman intestinal microbial ecosystemrdquo Applied Microbiologyand Biotechnology vol 39 no 2 pp 254ndash258 1993

[56] M Minekus M Smeets-Peeters A Bernalier et al ldquoAcomputer-controlled system to simulate conditions of thelarge intestine with peristaltic mixing water absorption andabsorption of fermentation productsrdquoAppliedMicrobiology andBiotechnology vol 53 no 1 pp 108ndash114 1999

[57] PDeBoever BDeplancke andWVerstraete ldquoFermentation bygut microbiota cultured in a simulator of the human intestinalmicrobial ecosystem is improved by supplementing a soygermpowderrdquo Journal of Nutrition vol 130 no 10 pp 2599ndash26062000

[58] C S Yang X Wang G Lu and S C Picinich ldquoCancerprevention by tea animal studies molecular mechanisms andhuman relevancerdquoNature Reviews Cancer vol 9 no 6 pp 429ndash439 2009

[59] R E Ley F Backhed P Turnbaugh C A Lozupone R DKnight and J I Gordon ldquoObesity alters gut microbial ecologyrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 102 no 31 pp 11070ndash11075 2005

[60] H Hara N Orita S Hatano et al ldquoEffect of tea polyphenols onfecal flora and fecal metabolic products of pigsrdquo The Journal ofVeterinary Medical Science vol 57 no 1 pp 45ndash49 1995

[61] N Ishihara D-C Chu S Akachi and L R Juneja ldquoImprove-ment of intestinal microflora balance and prevention of diges-tive and respiratory organ diseases in calves by green teaextractsrdquo Livestock Production Science vol 68 no 2-3 pp 217ndash229 2001

[62] P Dolara C Luceri C De Filippo et al ldquoRed wine polyphenolsinfluence carcinogenesis intestinal microflora oxidative dam-age and gene expression profiles of colonicmucosa in F344 ratsrdquoMutation Research-Fundamental and Molecular Mechanisms ofMutagenesis vol 591 no 1-2 pp 237ndash246 2005

[63] S Sembries G Dongowski K Mehrlander F Will and HDietrich ldquoPhysiological effects of extraction juices from applegrape and red beet pomaces in ratsrdquo Journal of Agricultural andFood Chemistry vol 54 no 26 pp 10269ndash10280 2006

[64] S Sembries G Dongowski G Jacobasch K Mehrlander FWill andH Dietrich ldquoEffects of dietary fibre-rich juice colloidsfrom apple pomace extraction juices on intestinal fermentationproducts and microbiota in ratsrdquo British Journal of Nutritionvol 90 no 3 pp 607ndash615 2003

[65] A Viveros S Chamorro M Pizarro I Arija C Centeno andA Brenes ldquoEffects of dietary polyphenol-rich grape productson intestinal microflora and gut morphology in broiler chicksrdquoPoultry Science vol 90 no 3 pp 566ndash578 2011

[66] A H Smith and R I Mackie ldquoEffect of condensed tannins onbacterial diversity andmetabolic activity in the rat gastrointesti-nal tractrdquo Applied and Environmental Microbiology vol 70 no2 pp 1104ndash1115 2004

[67] M Massot-Cladera T Perez-Berezo A Franch M Castelland F J Perez-Cano ldquoCocoa modulatory effect on rat faecalmicrobiota and colonic crosstalkrdquo Archives of Biochemistry andBiophysics vol 527 no 2 pp 105ndash112 2012

[68] M Larrosa M J Yanez-Gascon M V Selma et al ldquoEffectof a low dose of dietary resveratrol on colon microbiotainflammation and tissue damage in a DSS-induced colitis ratmodelrdquo Journal of Agricultural and Food Chemistry vol 57 no6 pp 2211ndash2220 2009

[69] A-L Molan Z Liu andM Kruger ldquoThe ability of blackcurrantextracts to positively modulate key markers of gastrointestinalfunction in ratsrdquoWorld Journal ofMicrobiologyampBiotechnologyvol 26 no 10 pp 1735ndash1743 2010

[70] A Lacombe R W Li D Klimis-Zacas et al ldquoLowbush wildblueberries have the potential to modify gut microbiota andxenobiotic metabolism in the rat colonrdquo PLoS ONE vol 8 no6 Article ID e67497 2013

[71] R Saad M R Rizkallah and R K Aziz ldquoGut Pharmacomicro-biomics the tip of an iceberg of complex interactions betweendrugs and gut-associated microbesrdquo Gut Pathogens vol 4 no1 article 16 2012

[72] E J J Van Velzen J A Westerhuis J P M van Duynhovenet al ldquoMultilevel data analysis of a crossover designed humannutritional intervention studyrdquo Journal of Proteome Researchvol 7 no 10 pp 4483ndash4491 2008

[73] T Okubo N Ishihara H Takahashi et al ldquoEffects of partiallyhydrolyzed guar gum intake on human intestinal microfloraand itsmetabolismrdquoBioscience Biotechnology andBiochemistryvol 58 no 8 pp 1364ndash1369 1994

[74] V Mai H A Katki H Harmsen et al ldquoEffects of a controlleddiet and black tea drinking on the fecalmicroflora compositionand the fecal bile acid profile of human volunteers in a double-blinded ramdomized feeding studyrdquo The Journal of Nutritionvol 134 no 2 pp 473ndash478 2004

[75] J-S Jin M Touyama T Hisada and Y Benno ldquoEffectsof green tea consumption on human fecal microbiota withspecial reference to Bifidobacterium speciesrdquoMicrobiology andImmunology vol 56 no 11 pp 729ndash739 2012

[76] J Yamakoshi S Tokutake M Kikuchi Y Kubota H Konishiand T Mitsuoka ldquoEffect of proantocyanidin -rich extract fromgrape seed on human fecal flora and fecalodorrdquo FASEB Journalvol 15 no 4 p A633 2001

[77] X Tzounis A Rodriguez-Mateos J Vulevic G R Gibson CKwik-Uribe and J P E Spencer ldquoPrebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomizedcontrolled double-blind crossover intervention studyrdquo TheAmerican Journal of Clinical Nutrition vol 93 no 1 pp 62ndash722011

[78] M I Queipo-Ortuno M Boto-Ordonez M Murri et alldquoInfluence of red wine polyphenols and ethanol on the gutmicrobiota ecology and biochemical biomarkersrdquo AmericanJournal of Clinical Nutrition vol 95 no 6 pp 1323ndash1334 2012

[79] K Shinohara Y Ohashi K Kawasumi A Terada and TFujisawa ldquoEffect of apple intake on fecal microbiota andmetabolites in humansrdquo Anaerobe vol 16 no 5 pp 510ndash5152010

[80] C I R Gill G J Mcdougall S Glidewell et al ldquoProfiling ofphenols in human fecal water after raspberry supplementationrdquoJournal of Agricultural and Food Chemistry vol 58 no 19 pp10389ndash10395 2010

[81] S Vendrame S Guglielmetti P Riso S Arioli D Klimis-Zacasand M Porrini ldquoSix-week consumption of a wild blueberry

BioMed Research International 15

powder drink increases Bifidobacteria in the human gutrdquoJournal of Agricultural and Food Chemistry vol 59 no 24 pp12815ndash12820 2011

[82] S Guglielmetti D Fracassetti V Taverniti et al ldquoDifferentialmodulation of human intestinal Bifidobacterium populationsafter consumption of a wild blueberry (Vaccinium angusti-folium) drinkrdquo Journal of Agricultural and Food Chemistry vol61 no 34 pp 8134ndash8140 2013

[83] T Clavel M Fallani P Lepage et al ldquoIsoflavones and func-tional foods alter the dominant intestinal microbiota in post-menopausal womenrdquo Journal of Nutrition vol 135 no 12 pp2786ndash2792 2005

[84] A Costabile A Klinder F Fava et al ldquoWhole-grain wheatbreakfast cereal has a prebiotic effect on the human gut micro-biota a double-blind placebo-controlled crossover studyrdquoBritish Journal of Nutrition vol 99 no 1 pp 110ndash120 2008

[85] A L Carvalho-Wells K Helmolz C Nodet et al ldquoDetermina-tion of the in vivo prebiotic potential of a maize-based wholegrain breakfast cereal a human feeding studyrdquo British Journalof Nutrition vol 104 no 9 pp 1353ndash1356 2010

[86] A Cuervo L Valdes N Salazar et al ldquoPilot study of diet andmicrobiota interactive associations of fibers and polyphenolswith human intestinal bacteriardquo Journal of Agricultural andFood Chemistry vol 62 no 23 pp 5330ndash5336 2014

[87] M Jaquet I Rochat J Moulin C Cavin and R BibilonildquoImpact of coffee consumption on the gut microbiota a humanvolunteer studyrdquo International Journal of FoodMicrobiology vol130 no 2 pp 117ndash121 2009

Submit your manuscripts athttpwwwhindawicom

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Page 12: Review Article A Survey of Modulation of Gut Microbiota by ...downloads.hindawi.com/journals/bmri/2015/850902.pdf · Review Article A Survey of Modulation of Gut Microbiota by Dietary

12 BioMed Research International

be essential in order to identify genes and micro-organismsinvolved in polyphenol (in)activation and conversion andthus to elucidate the implications of diet on the modulationof microbiota for delivering health benefits

Functional foods are considered to enhance the protectiveeffects against diseases derived from some food componentsIn the last decades dairy fermented foods have probablybeen one of the most-developed functional products andhave deserved intensive research In this expansion dairyfermented foods have been supplemented with fruits cerealsand other stuffs of plant origin all of which represent a highpercentage of the current market of the dairy industry Theseproducts have a healthy appeal which attracts consumersThus fruit juicesconcentrates and prepared fruits (in theform of pieces pulp and even flour) have been successfullyincorporated in dairy fermented foods as sources of prebioticfibers and phytochemicals Among these phytochemicalspresent in plant-derived foods polyphenols have gainedmuch interest due to their diverse potential beneficial effectsin human health The supplementation of dairy fermentedproducts with rich-polyphenolic stuffs (phenolic extractsphenolic-enriched fractions etc) seems to be an effectivetechnological option to improve the benefits of these productsin the balance of the intestinal microbiota due not only to theaction of the probiotics but also to the potential modulationeffects exerted by polyphenols as it has been described in thisreview Further research in this area will aim to accomplishthe benefits of both probiotic strains and polyphenols inrelation to gut health

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors of this review were funded by the SpanishMINECO through different projects (AGL2012-40172-C02-01 AGL2010-17499 and BFU2012-35228) and the CON-SOLIDER INGENIO 2010 programme (project FUN-C-FOOD CSD2007-063) as well as Comunidad de Madrid(project ALIBIRD P2009AGR-1469) Montserrat Duenaswould like to thank the Spanish ldquoRamon y Cajalrdquo Programmefor a contract

References

[1] S E Power P W OrsquoToole C Stanton R P Ross and GF Fitzgerald ldquoIntestinal microbiota diet and healthrdquo BritishJournal of Nutrition vol 111 no 3 pp 387ndash402 2014

[2] PDeCruz L Prideaux JWagner et al ldquoCharacterization of thegastrointestinal microbiota in health and inflammatory boweldiseaserdquo Inflammatory Bowel Diseases vol 18 no 2 pp 372ndash390 2012

[3] A Kramer S Bekeschus B M Broker H Schleibinger BRazavi and O Assadian ldquoMaintaining health by balancingmicrobial exposure and prevention of infection the hygienehypothesis versus the hypothesis of early immune challengerdquoJournal of Hospital Infection vol 83 no 1 pp S29ndashS34 2013

[4] M Rescigno ldquoIntestinal microbiota and its effects on theimmune systemrdquo Cellular Microbiology vol 16 no 7 pp 1004ndash1013 2014

[5] M G L Hertog E J M Feskens P C H HollmanM B Katanand D Kromhout ldquoDietary antioxidant flavonoids and risk ofcoronary heart disease the Zutphen Elderly StudyrdquoThe Lancetvol 342 no 8878 pp 1007ndash1011 1993

[6] I C W Arts and P C H Hollman ldquoPolyphenols and diseaserisk in epidemiologic studiesrdquoThe American Journal of ClinicalNutrition vol 81 no 1 pp 317Sndash325S 2009

[7] D del Rio A Rodriguez-Mateos J P E Spencer M TognoliniG Borges and A Crozier ldquoDietary (poly)phenolics in humanhealth structures bioavailability and evidence of protectiveeffects against chronic diseasesrdquo Antioxidants amp Redox Signal-ing vol 18 no 14 pp 1818ndash1892 2013

[8] F Perez-Vizcaino and J Duarte ldquoFlavonols and cardiovasculardiseaserdquo Molecular Aspects of Medicine vol 31 no 6 pp 478ndash494 2010

[9] J P E Spencer K Vafeiadou R J Williams and D VauzourldquoNeuroinflammation modulation by flavonoids and mecha-nisms of actionrdquo Molecular Aspects of Medicine vol 33 no 1pp 83ndash97 2012

[10] J M Laparra and Y Sanz ldquoInteractions of gut microbiota withfunctional food components and nutraceuticalsrdquo Pharmacolog-ical Research vol 61 no 3 pp 219ndash225 2010

[11] X He M L Marco and C M Slupsky ldquoEmerging aspects offood and nutrition on gut microbiotardquo Journal of Agriculturaland Food Chemistry vol 61 no 40 pp 9559ndash9574 2013

[12] D Hervert-Hernandez and I Goni ldquoDietary polyphenols andhuman gut microbiota a reviewrdquo Food Reviews Internationalvol 27 no 2 pp 154ndash169 2011

[13] K M Tuohy L Conterno M Gasperotti and R Viola ldquoUp-regulating the human intestinal microbiome using whole plantfoods polyphenols andor fiberrdquo Journal of Agricultural andFood Chemistry vol 60 no 36 pp 8776ndash8782 2012

[14] U Etxeberria A Fernandez-Quintela F I Milagro L AguirreJ A Martınez and M P Portillo ldquoImpact of polyphenols andpolyphenol-rich dietary sources on gut microbiota composi-tionrdquo Journal of Agricultural and Food Chemistry vol 61 no 40pp 9517ndash9533 2013

[15] F Cardona C Andres-Lacueva S Tulipani F J Tinahonesand M I Queipo-Ortuno ldquoBenefits of polyphenols on gutmicrobiota and implications in human healthrdquo Journal ofNutritional Biochemistry vol 24 no 8 pp 1415ndash1422 2013

[16] M V Selma J C Espın and F A Tomas-Barberan ldquoInteractionbetween phenolics and gut microbiota role in human healthrdquoJournal of Agricultural and Food Chemistry vol 57 no 15 pp6485ndash6501 2009

[17] T RequenaMMonagasM A Pozo-Bayon et al ldquoPerspectivesof the potential implications ofwine polyphenols on humanoraland gut microbiotardquo Trends in Food Science amp Technology vol21 no 7 pp 332ndash344 2010

[18] J Van Duynhoven E E Vaughan F van Dorsten et alldquoInteractions of black tea polyphenols with human gut micro-biota implications for gut and cardiovascular health1-4rdquo TheAmerican Journal of Clinical Nutrition vol 98 no 6 pp 1631Sndash1641S 2013

[19] SMoco F-P JMartin and S Rezzi ldquoMetabolomics view on gutmicrobiome modulation by polyphenol-rich foodsrdquo Journal ofProteome Research vol 11 no 10 pp 4781ndash4790 2012

BioMed Research International 13

[20] R K Buddington and P T Sangild ldquoCompanion animalssymposium development of the mammalian gastrointestinaltract the resident microbiota and the role of diet in early liferdquoJournal of Animal Science vol 89 no 5 pp 1506ndash1519 2011

[21] K Tiihonen A C Ouwehand and N Rautonen ldquoHumanintestinal microbiota and healthy ageingrdquo Ageing ResearchReviews vol 9 no 2 pp 107ndash116 2010

[22] D Mariat O Firmesse F Levenez et al ldquoThe firmicutesbacteroidetes ratio of the human microbiota changes with agerdquoBMCMicrobiology vol 9 article 123 2009

[23] M Arumugam J Raes E Pelletier et al ldquoEnterotypes of thehuman gutmicrobiomerdquoNature vol 473 no 7346 pp 174ndash1802011

[24] G D Wu J Chen C Hoffmann et al ldquoLinking long-termdietary patterns with gut microbial enterotypesrdquo Science vol334 no 6052 pp 105ndash108 2011

[25] I B JefferyM J Claesson PWOrsquoToole and F Shanahan ldquoCat-egorization of the gut microbiota enterotypes or gradientsrdquoNature Reviews Microbiology vol 10 no 9 pp 591ndash592 2012

[26] WM de Vos andM Nieuwdorp ldquoGenomics a gut predictionrdquoNature vol 498 no 7452 pp 48ndash49 2013

[27] P B Eckburg E M Bik C N Bernstein et al ldquoMicrobiologydiversity of the human intestinal microbial florardquo Science vol308 no 5728 pp 1635ndash1638 2005

[28] E G Zoetendal C T Collier S Koike R I Mackie and H RGaskins ldquoMolecular ecological analysis of the gastrointestinalmicrobiota a reviewrdquo Journal of Nutrition vol 134 no 2 pp465ndash472 2004

[29] M H Fraher PW OrsquoToole and E MM Quigley ldquoTechniquesused to characterize the gut microbiota a guide for the clini-cianrdquo Nature Reviews Gastroenterology and Hepatology vol 9no 6 pp 312ndash322 2012

[30] R A Kemperman S Bolca L C Roger and E E VaughanldquoNovel approaches for analysing gut microbes and dietarypolyphenols challenges and opportunitiesrdquo Microbiology vol156 no 11 pp 3224ndash3231 2010

[31] R A Kemperman G Gross S Mondot et al ldquoImpact ofpolyphenols from black tea and red winegrape juice on a gutmodel microbiomerdquo Food Research International vol 53 no 2pp 659ndash669 2013

[32] M N Clifford ldquoDiet-derived phenols in plasma and tissues andtheir implications for healthrdquo Planta Medica vol 70 no 12 pp1103ndash1114 2004

[33] A Crozier D del Rio and M N Clifford ldquoBioavailability ofdietary flavonoids and phenolic compoundsrdquoMolecular Aspectsof Medicine vol 31 no 6 pp 446ndash467 2010

[34] A J Day M S Dupont S Ridley et al ldquoDeglycosylation offlavonoid and isoflavonoid glycosides by human small intestineand liver beta-glucosidase activityrdquo FEBS Letters vol 436 no 1pp 71ndash75 1998

[35] A J Day F J Canada J C Dıaz et al ldquoDietary flavonoid andisoflavone glycosides are hydrolysed by the lactase site of lactasephlorizin hydrolaserdquo FEBS Letters vol 468 no 2-3 pp 166ndash1702000

[36] A Scalbert and G Williamson ldquoDietary intake and bioavail-ability of polyphenolsrdquo Journal of Nutrition vol 130 no 8 pp2073Sndash2085S 2000

[37] A R Rechner G Kuhnle H Hu et al ldquoThe metabolism ofdietary polyphenols and the relevance to circulating levels ofconjugated metabolitesrdquo Free Radical Research vol 36 no 11pp 1229ndash1241 2002

[38] A-M Aura K A OrsquoLeary G Williamson et al ldquoQuercetinderivatives are deconjugated and converted to hydroxypheny-lacetic acids but not methylated by human fecal flora in vitrordquoJournal of Agricultural and Food Chemistry vol 50 no 6 pp1725ndash1730 2002

[39] A-M Aura ldquoMicrobial metabolism of dietary phenolic com-pounds in the colonrdquo Phytochemistry Reviews vol 7 no 3 pp407ndash429 2008

[40] M Monagas M Urpi-Sarda F Sanchez-Patan et al ldquoInsightsinto themetabolism andmicrobial biotransformation of dietaryflavan-3-ols and the bioactivity of their metabolitesrdquo Food andFunction vol 1 no 3 pp 233ndash253 2010

[41] GWilliamson andMNClifford ldquoColonicmetabolites of berrypolyphenols the missing link to biological activityrdquo BritishJournal of Nutrition vol 104 no 3 pp S48ndashS66 2010

[42] D M Jacobs E Gaudier J van Duynhoven and E E VaughanldquoNon-digestible food ingredients colonic microbiota and theimpact on gut health and immunity a role for metabolomicsrdquoCurrent Drug Metabolism vol 10 no 1 pp 41ndash54 2009

[43] S Bolca S Possemiers V Maervoet et al ldquoMicrobial anddietary factors associatedwith the 8-prenylnaringenin producerphenotype a dietary intervention trial with fifty healthy post-menopausal Caucasian womenrdquo British Journal of Nutritionvol 98 no 5 pp 950ndash959 2007

[44] X Tzounis J Vulevic G G C Kuhnle et al ldquoFlavanolmonomer-induced changes to the human faecal microflorardquoBritish Journal of Nutrition vol 99 no 4 pp 782ndash792 2008

[45] M Hidalgo M J Oruna-Concha S Kolida et al ldquoMetabolismof anthocyanins by human gut microflora and their influenceon gut bacterial growthrdquo Journal of Agricultural and FoodChemistry vol 60 no 15 pp 3882ndash3890 2012

[46] A L Molan M A Lila J Mawson and S De ldquoIn vitroand in vivo evaluation of the prebiotic activity of water-soluble blueberry extractsrdquo World Journal of Microbiology andBiotechnology vol 25 no 7 pp 1243ndash1249 2009

[47] D Bialonska P Ramnani S G Kasimsetty K R Muntha GR Gibson and D Ferreira ldquoThe influence of pomegranate by-product and punicalagins on selected groups of human intesti-nal microbiotardquo International Journal of FoodMicrobiology vol140 no 2-3 pp 175ndash182 2010

[48] G Mandalari R M Faulks C Bisignano K W Waldron ANarbad and M S J Wickham ldquoIn vitro evaluation of theprebiotic properties of almond skins (Amygdalus communisL)rdquoFEMS Microbiology Letters vol 304 no 2 pp 116ndash122 2010

[49] V Fogliano M L Corollaro P Vitaglione et al ldquoIn vitro bioac-cessibility and gut biotransformation of polyphenols present inthe water-insoluble cocoa fractionrdquoMolecular Nutritionamp FoodResearch vol 55 supplement 1 pp S44ndashS55 2011

[50] M J Pozuelo A Agis-Torres D Hervert-Hernandez etal ldquoGrape antioxidant dietary fiber stimulates Lactobacillusgrowth in rat cecumrdquo Journal of Food Science vol 77 no 2 ppH59ndashH62 2012

[51] C Cueva F Sanchez-Patan M Monagas et al ldquoIn vitrofermentation of grape seed flavan-3-ol fractions by humanfaecal microbiota changes in microbial groups and phenolicmetabolitesrdquo FEMSMicrobiology Ecology vol 83 no 3 pp 792ndash805 2013

[52] F Sanchez-Patan C CuevaMMonagas et al ldquoIn vitro fermen-tation of a red wine extract by human gut microbiota changesin microbial groups and formation of phenolic metabolitesrdquoJournal of Agricultural and Food Chemistry vol 60 no 9 pp2136ndash2147 2012

14 BioMed Research International

[53] E Barroso F Sanchez-Patan P J Martın-Alvarez et al ldquoLacto-bacillus plantarum IFPL935 favors the initial metabolism of redwine polyphenols when added to a colonic microbiotardquo Journalof Agricultural and Food Chemistry vol 61 no 42 pp 10163ndash10172 2013

[54] G R Gibson J H Cummings and G T Macfarlane ldquoUse ofa three-stage continuous culture system to study the effect ofmucin on dissimilatory sulfate reduction and methanogenesisby mixed populations of human gut bacteriardquo Applied andEnvironmentalMicrobiology vol 54 no 11 pp 2750ndash2755 1988

[55] KMollyMVandeWoestyne andWVerstraete ldquoDevelopmentof a 5-step multi-chamber reactor as a simulation of thehuman intestinal microbial ecosystemrdquo Applied Microbiologyand Biotechnology vol 39 no 2 pp 254ndash258 1993

[56] M Minekus M Smeets-Peeters A Bernalier et al ldquoAcomputer-controlled system to simulate conditions of thelarge intestine with peristaltic mixing water absorption andabsorption of fermentation productsrdquoAppliedMicrobiology andBiotechnology vol 53 no 1 pp 108ndash114 1999

[57] PDeBoever BDeplancke andWVerstraete ldquoFermentation bygut microbiota cultured in a simulator of the human intestinalmicrobial ecosystem is improved by supplementing a soygermpowderrdquo Journal of Nutrition vol 130 no 10 pp 2599ndash26062000

[58] C S Yang X Wang G Lu and S C Picinich ldquoCancerprevention by tea animal studies molecular mechanisms andhuman relevancerdquoNature Reviews Cancer vol 9 no 6 pp 429ndash439 2009

[59] R E Ley F Backhed P Turnbaugh C A Lozupone R DKnight and J I Gordon ldquoObesity alters gut microbial ecologyrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 102 no 31 pp 11070ndash11075 2005

[60] H Hara N Orita S Hatano et al ldquoEffect of tea polyphenols onfecal flora and fecal metabolic products of pigsrdquo The Journal ofVeterinary Medical Science vol 57 no 1 pp 45ndash49 1995

[61] N Ishihara D-C Chu S Akachi and L R Juneja ldquoImprove-ment of intestinal microflora balance and prevention of diges-tive and respiratory organ diseases in calves by green teaextractsrdquo Livestock Production Science vol 68 no 2-3 pp 217ndash229 2001

[62] P Dolara C Luceri C De Filippo et al ldquoRed wine polyphenolsinfluence carcinogenesis intestinal microflora oxidative dam-age and gene expression profiles of colonicmucosa in F344 ratsrdquoMutation Research-Fundamental and Molecular Mechanisms ofMutagenesis vol 591 no 1-2 pp 237ndash246 2005

[63] S Sembries G Dongowski K Mehrlander F Will and HDietrich ldquoPhysiological effects of extraction juices from applegrape and red beet pomaces in ratsrdquo Journal of Agricultural andFood Chemistry vol 54 no 26 pp 10269ndash10280 2006

[64] S Sembries G Dongowski G Jacobasch K Mehrlander FWill andH Dietrich ldquoEffects of dietary fibre-rich juice colloidsfrom apple pomace extraction juices on intestinal fermentationproducts and microbiota in ratsrdquo British Journal of Nutritionvol 90 no 3 pp 607ndash615 2003

[65] A Viveros S Chamorro M Pizarro I Arija C Centeno andA Brenes ldquoEffects of dietary polyphenol-rich grape productson intestinal microflora and gut morphology in broiler chicksrdquoPoultry Science vol 90 no 3 pp 566ndash578 2011

[66] A H Smith and R I Mackie ldquoEffect of condensed tannins onbacterial diversity andmetabolic activity in the rat gastrointesti-nal tractrdquo Applied and Environmental Microbiology vol 70 no2 pp 1104ndash1115 2004

[67] M Massot-Cladera T Perez-Berezo A Franch M Castelland F J Perez-Cano ldquoCocoa modulatory effect on rat faecalmicrobiota and colonic crosstalkrdquo Archives of Biochemistry andBiophysics vol 527 no 2 pp 105ndash112 2012

[68] M Larrosa M J Yanez-Gascon M V Selma et al ldquoEffectof a low dose of dietary resveratrol on colon microbiotainflammation and tissue damage in a DSS-induced colitis ratmodelrdquo Journal of Agricultural and Food Chemistry vol 57 no6 pp 2211ndash2220 2009

[69] A-L Molan Z Liu andM Kruger ldquoThe ability of blackcurrantextracts to positively modulate key markers of gastrointestinalfunction in ratsrdquoWorld Journal ofMicrobiologyampBiotechnologyvol 26 no 10 pp 1735ndash1743 2010

[70] A Lacombe R W Li D Klimis-Zacas et al ldquoLowbush wildblueberries have the potential to modify gut microbiota andxenobiotic metabolism in the rat colonrdquo PLoS ONE vol 8 no6 Article ID e67497 2013

[71] R Saad M R Rizkallah and R K Aziz ldquoGut Pharmacomicro-biomics the tip of an iceberg of complex interactions betweendrugs and gut-associated microbesrdquo Gut Pathogens vol 4 no1 article 16 2012

[72] E J J Van Velzen J A Westerhuis J P M van Duynhovenet al ldquoMultilevel data analysis of a crossover designed humannutritional intervention studyrdquo Journal of Proteome Researchvol 7 no 10 pp 4483ndash4491 2008

[73] T Okubo N Ishihara H Takahashi et al ldquoEffects of partiallyhydrolyzed guar gum intake on human intestinal microfloraand itsmetabolismrdquoBioscience Biotechnology andBiochemistryvol 58 no 8 pp 1364ndash1369 1994

[74] V Mai H A Katki H Harmsen et al ldquoEffects of a controlleddiet and black tea drinking on the fecalmicroflora compositionand the fecal bile acid profile of human volunteers in a double-blinded ramdomized feeding studyrdquo The Journal of Nutritionvol 134 no 2 pp 473ndash478 2004

[75] J-S Jin M Touyama T Hisada and Y Benno ldquoEffectsof green tea consumption on human fecal microbiota withspecial reference to Bifidobacterium speciesrdquoMicrobiology andImmunology vol 56 no 11 pp 729ndash739 2012

[76] J Yamakoshi S Tokutake M Kikuchi Y Kubota H Konishiand T Mitsuoka ldquoEffect of proantocyanidin -rich extract fromgrape seed on human fecal flora and fecalodorrdquo FASEB Journalvol 15 no 4 p A633 2001

[77] X Tzounis A Rodriguez-Mateos J Vulevic G R Gibson CKwik-Uribe and J P E Spencer ldquoPrebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomizedcontrolled double-blind crossover intervention studyrdquo TheAmerican Journal of Clinical Nutrition vol 93 no 1 pp 62ndash722011

[78] M I Queipo-Ortuno M Boto-Ordonez M Murri et alldquoInfluence of red wine polyphenols and ethanol on the gutmicrobiota ecology and biochemical biomarkersrdquo AmericanJournal of Clinical Nutrition vol 95 no 6 pp 1323ndash1334 2012

[79] K Shinohara Y Ohashi K Kawasumi A Terada and TFujisawa ldquoEffect of apple intake on fecal microbiota andmetabolites in humansrdquo Anaerobe vol 16 no 5 pp 510ndash5152010

[80] C I R Gill G J Mcdougall S Glidewell et al ldquoProfiling ofphenols in human fecal water after raspberry supplementationrdquoJournal of Agricultural and Food Chemistry vol 58 no 19 pp10389ndash10395 2010

[81] S Vendrame S Guglielmetti P Riso S Arioli D Klimis-Zacasand M Porrini ldquoSix-week consumption of a wild blueberry

BioMed Research International 15

powder drink increases Bifidobacteria in the human gutrdquoJournal of Agricultural and Food Chemistry vol 59 no 24 pp12815ndash12820 2011

[82] S Guglielmetti D Fracassetti V Taverniti et al ldquoDifferentialmodulation of human intestinal Bifidobacterium populationsafter consumption of a wild blueberry (Vaccinium angusti-folium) drinkrdquo Journal of Agricultural and Food Chemistry vol61 no 34 pp 8134ndash8140 2013

[83] T Clavel M Fallani P Lepage et al ldquoIsoflavones and func-tional foods alter the dominant intestinal microbiota in post-menopausal womenrdquo Journal of Nutrition vol 135 no 12 pp2786ndash2792 2005

[84] A Costabile A Klinder F Fava et al ldquoWhole-grain wheatbreakfast cereal has a prebiotic effect on the human gut micro-biota a double-blind placebo-controlled crossover studyrdquoBritish Journal of Nutrition vol 99 no 1 pp 110ndash120 2008

[85] A L Carvalho-Wells K Helmolz C Nodet et al ldquoDetermina-tion of the in vivo prebiotic potential of a maize-based wholegrain breakfast cereal a human feeding studyrdquo British Journalof Nutrition vol 104 no 9 pp 1353ndash1356 2010

[86] A Cuervo L Valdes N Salazar et al ldquoPilot study of diet andmicrobiota interactive associations of fibers and polyphenolswith human intestinal bacteriardquo Journal of Agricultural andFood Chemistry vol 62 no 23 pp 5330ndash5336 2014

[87] M Jaquet I Rochat J Moulin C Cavin and R BibilonildquoImpact of coffee consumption on the gut microbiota a humanvolunteer studyrdquo International Journal of FoodMicrobiology vol130 no 2 pp 117ndash121 2009

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

Volume 2014

Zoology

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Molecular Biology International

GenomicsInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Signal TransductionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Evolutionary BiologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Genetics Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Virolog y

Hindawi Publishing Corporationhttpwwwhindawicom

Nucleic AcidsJournal of

Volume 2014

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Enzyme Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Microbiology

Page 13: Review Article A Survey of Modulation of Gut Microbiota by ...downloads.hindawi.com/journals/bmri/2015/850902.pdf · Review Article A Survey of Modulation of Gut Microbiota by Dietary

BioMed Research International 13

[20] R K Buddington and P T Sangild ldquoCompanion animalssymposium development of the mammalian gastrointestinaltract the resident microbiota and the role of diet in early liferdquoJournal of Animal Science vol 89 no 5 pp 1506ndash1519 2011

[21] K Tiihonen A C Ouwehand and N Rautonen ldquoHumanintestinal microbiota and healthy ageingrdquo Ageing ResearchReviews vol 9 no 2 pp 107ndash116 2010

[22] D Mariat O Firmesse F Levenez et al ldquoThe firmicutesbacteroidetes ratio of the human microbiota changes with agerdquoBMCMicrobiology vol 9 article 123 2009

[23] M Arumugam J Raes E Pelletier et al ldquoEnterotypes of thehuman gutmicrobiomerdquoNature vol 473 no 7346 pp 174ndash1802011

[24] G D Wu J Chen C Hoffmann et al ldquoLinking long-termdietary patterns with gut microbial enterotypesrdquo Science vol334 no 6052 pp 105ndash108 2011

[25] I B JefferyM J Claesson PWOrsquoToole and F Shanahan ldquoCat-egorization of the gut microbiota enterotypes or gradientsrdquoNature Reviews Microbiology vol 10 no 9 pp 591ndash592 2012

[26] WM de Vos andM Nieuwdorp ldquoGenomics a gut predictionrdquoNature vol 498 no 7452 pp 48ndash49 2013

[27] P B Eckburg E M Bik C N Bernstein et al ldquoMicrobiologydiversity of the human intestinal microbial florardquo Science vol308 no 5728 pp 1635ndash1638 2005

[28] E G Zoetendal C T Collier S Koike R I Mackie and H RGaskins ldquoMolecular ecological analysis of the gastrointestinalmicrobiota a reviewrdquo Journal of Nutrition vol 134 no 2 pp465ndash472 2004

[29] M H Fraher PW OrsquoToole and E MM Quigley ldquoTechniquesused to characterize the gut microbiota a guide for the clini-cianrdquo Nature Reviews Gastroenterology and Hepatology vol 9no 6 pp 312ndash322 2012

[30] R A Kemperman S Bolca L C Roger and E E VaughanldquoNovel approaches for analysing gut microbes and dietarypolyphenols challenges and opportunitiesrdquo Microbiology vol156 no 11 pp 3224ndash3231 2010

[31] R A Kemperman G Gross S Mondot et al ldquoImpact ofpolyphenols from black tea and red winegrape juice on a gutmodel microbiomerdquo Food Research International vol 53 no 2pp 659ndash669 2013

[32] M N Clifford ldquoDiet-derived phenols in plasma and tissues andtheir implications for healthrdquo Planta Medica vol 70 no 12 pp1103ndash1114 2004

[33] A Crozier D del Rio and M N Clifford ldquoBioavailability ofdietary flavonoids and phenolic compoundsrdquoMolecular Aspectsof Medicine vol 31 no 6 pp 446ndash467 2010

[34] A J Day M S Dupont S Ridley et al ldquoDeglycosylation offlavonoid and isoflavonoid glycosides by human small intestineand liver beta-glucosidase activityrdquo FEBS Letters vol 436 no 1pp 71ndash75 1998

[35] A J Day F J Canada J C Dıaz et al ldquoDietary flavonoid andisoflavone glycosides are hydrolysed by the lactase site of lactasephlorizin hydrolaserdquo FEBS Letters vol 468 no 2-3 pp 166ndash1702000

[36] A Scalbert and G Williamson ldquoDietary intake and bioavail-ability of polyphenolsrdquo Journal of Nutrition vol 130 no 8 pp2073Sndash2085S 2000

[37] A R Rechner G Kuhnle H Hu et al ldquoThe metabolism ofdietary polyphenols and the relevance to circulating levels ofconjugated metabolitesrdquo Free Radical Research vol 36 no 11pp 1229ndash1241 2002

[38] A-M Aura K A OrsquoLeary G Williamson et al ldquoQuercetinderivatives are deconjugated and converted to hydroxypheny-lacetic acids but not methylated by human fecal flora in vitrordquoJournal of Agricultural and Food Chemistry vol 50 no 6 pp1725ndash1730 2002

[39] A-M Aura ldquoMicrobial metabolism of dietary phenolic com-pounds in the colonrdquo Phytochemistry Reviews vol 7 no 3 pp407ndash429 2008

[40] M Monagas M Urpi-Sarda F Sanchez-Patan et al ldquoInsightsinto themetabolism andmicrobial biotransformation of dietaryflavan-3-ols and the bioactivity of their metabolitesrdquo Food andFunction vol 1 no 3 pp 233ndash253 2010

[41] GWilliamson andMNClifford ldquoColonicmetabolites of berrypolyphenols the missing link to biological activityrdquo BritishJournal of Nutrition vol 104 no 3 pp S48ndashS66 2010

[42] D M Jacobs E Gaudier J van Duynhoven and E E VaughanldquoNon-digestible food ingredients colonic microbiota and theimpact on gut health and immunity a role for metabolomicsrdquoCurrent Drug Metabolism vol 10 no 1 pp 41ndash54 2009

[43] S Bolca S Possemiers V Maervoet et al ldquoMicrobial anddietary factors associatedwith the 8-prenylnaringenin producerphenotype a dietary intervention trial with fifty healthy post-menopausal Caucasian womenrdquo British Journal of Nutritionvol 98 no 5 pp 950ndash959 2007

[44] X Tzounis J Vulevic G G C Kuhnle et al ldquoFlavanolmonomer-induced changes to the human faecal microflorardquoBritish Journal of Nutrition vol 99 no 4 pp 782ndash792 2008

[45] M Hidalgo M J Oruna-Concha S Kolida et al ldquoMetabolismof anthocyanins by human gut microflora and their influenceon gut bacterial growthrdquo Journal of Agricultural and FoodChemistry vol 60 no 15 pp 3882ndash3890 2012

[46] A L Molan M A Lila J Mawson and S De ldquoIn vitroand in vivo evaluation of the prebiotic activity of water-soluble blueberry extractsrdquo World Journal of Microbiology andBiotechnology vol 25 no 7 pp 1243ndash1249 2009

[47] D Bialonska P Ramnani S G Kasimsetty K R Muntha GR Gibson and D Ferreira ldquoThe influence of pomegranate by-product and punicalagins on selected groups of human intesti-nal microbiotardquo International Journal of FoodMicrobiology vol140 no 2-3 pp 175ndash182 2010

[48] G Mandalari R M Faulks C Bisignano K W Waldron ANarbad and M S J Wickham ldquoIn vitro evaluation of theprebiotic properties of almond skins (Amygdalus communisL)rdquoFEMS Microbiology Letters vol 304 no 2 pp 116ndash122 2010

[49] V Fogliano M L Corollaro P Vitaglione et al ldquoIn vitro bioac-cessibility and gut biotransformation of polyphenols present inthe water-insoluble cocoa fractionrdquoMolecular Nutritionamp FoodResearch vol 55 supplement 1 pp S44ndashS55 2011

[50] M J Pozuelo A Agis-Torres D Hervert-Hernandez etal ldquoGrape antioxidant dietary fiber stimulates Lactobacillusgrowth in rat cecumrdquo Journal of Food Science vol 77 no 2 ppH59ndashH62 2012

[51] C Cueva F Sanchez-Patan M Monagas et al ldquoIn vitrofermentation of grape seed flavan-3-ol fractions by humanfaecal microbiota changes in microbial groups and phenolicmetabolitesrdquo FEMSMicrobiology Ecology vol 83 no 3 pp 792ndash805 2013

[52] F Sanchez-Patan C CuevaMMonagas et al ldquoIn vitro fermen-tation of a red wine extract by human gut microbiota changesin microbial groups and formation of phenolic metabolitesrdquoJournal of Agricultural and Food Chemistry vol 60 no 9 pp2136ndash2147 2012

14 BioMed Research International

[53] E Barroso F Sanchez-Patan P J Martın-Alvarez et al ldquoLacto-bacillus plantarum IFPL935 favors the initial metabolism of redwine polyphenols when added to a colonic microbiotardquo Journalof Agricultural and Food Chemistry vol 61 no 42 pp 10163ndash10172 2013

[54] G R Gibson J H Cummings and G T Macfarlane ldquoUse ofa three-stage continuous culture system to study the effect ofmucin on dissimilatory sulfate reduction and methanogenesisby mixed populations of human gut bacteriardquo Applied andEnvironmentalMicrobiology vol 54 no 11 pp 2750ndash2755 1988

[55] KMollyMVandeWoestyne andWVerstraete ldquoDevelopmentof a 5-step multi-chamber reactor as a simulation of thehuman intestinal microbial ecosystemrdquo Applied Microbiologyand Biotechnology vol 39 no 2 pp 254ndash258 1993

[56] M Minekus M Smeets-Peeters A Bernalier et al ldquoAcomputer-controlled system to simulate conditions of thelarge intestine with peristaltic mixing water absorption andabsorption of fermentation productsrdquoAppliedMicrobiology andBiotechnology vol 53 no 1 pp 108ndash114 1999

[57] PDeBoever BDeplancke andWVerstraete ldquoFermentation bygut microbiota cultured in a simulator of the human intestinalmicrobial ecosystem is improved by supplementing a soygermpowderrdquo Journal of Nutrition vol 130 no 10 pp 2599ndash26062000

[58] C S Yang X Wang G Lu and S C Picinich ldquoCancerprevention by tea animal studies molecular mechanisms andhuman relevancerdquoNature Reviews Cancer vol 9 no 6 pp 429ndash439 2009

[59] R E Ley F Backhed P Turnbaugh C A Lozupone R DKnight and J I Gordon ldquoObesity alters gut microbial ecologyrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 102 no 31 pp 11070ndash11075 2005

[60] H Hara N Orita S Hatano et al ldquoEffect of tea polyphenols onfecal flora and fecal metabolic products of pigsrdquo The Journal ofVeterinary Medical Science vol 57 no 1 pp 45ndash49 1995

[61] N Ishihara D-C Chu S Akachi and L R Juneja ldquoImprove-ment of intestinal microflora balance and prevention of diges-tive and respiratory organ diseases in calves by green teaextractsrdquo Livestock Production Science vol 68 no 2-3 pp 217ndash229 2001

[62] P Dolara C Luceri C De Filippo et al ldquoRed wine polyphenolsinfluence carcinogenesis intestinal microflora oxidative dam-age and gene expression profiles of colonicmucosa in F344 ratsrdquoMutation Research-Fundamental and Molecular Mechanisms ofMutagenesis vol 591 no 1-2 pp 237ndash246 2005

[63] S Sembries G Dongowski K Mehrlander F Will and HDietrich ldquoPhysiological effects of extraction juices from applegrape and red beet pomaces in ratsrdquo Journal of Agricultural andFood Chemistry vol 54 no 26 pp 10269ndash10280 2006

[64] S Sembries G Dongowski G Jacobasch K Mehrlander FWill andH Dietrich ldquoEffects of dietary fibre-rich juice colloidsfrom apple pomace extraction juices on intestinal fermentationproducts and microbiota in ratsrdquo British Journal of Nutritionvol 90 no 3 pp 607ndash615 2003

[65] A Viveros S Chamorro M Pizarro I Arija C Centeno andA Brenes ldquoEffects of dietary polyphenol-rich grape productson intestinal microflora and gut morphology in broiler chicksrdquoPoultry Science vol 90 no 3 pp 566ndash578 2011

[66] A H Smith and R I Mackie ldquoEffect of condensed tannins onbacterial diversity andmetabolic activity in the rat gastrointesti-nal tractrdquo Applied and Environmental Microbiology vol 70 no2 pp 1104ndash1115 2004

[67] M Massot-Cladera T Perez-Berezo A Franch M Castelland F J Perez-Cano ldquoCocoa modulatory effect on rat faecalmicrobiota and colonic crosstalkrdquo Archives of Biochemistry andBiophysics vol 527 no 2 pp 105ndash112 2012

[68] M Larrosa M J Yanez-Gascon M V Selma et al ldquoEffectof a low dose of dietary resveratrol on colon microbiotainflammation and tissue damage in a DSS-induced colitis ratmodelrdquo Journal of Agricultural and Food Chemistry vol 57 no6 pp 2211ndash2220 2009

[69] A-L Molan Z Liu andM Kruger ldquoThe ability of blackcurrantextracts to positively modulate key markers of gastrointestinalfunction in ratsrdquoWorld Journal ofMicrobiologyampBiotechnologyvol 26 no 10 pp 1735ndash1743 2010

[70] A Lacombe R W Li D Klimis-Zacas et al ldquoLowbush wildblueberries have the potential to modify gut microbiota andxenobiotic metabolism in the rat colonrdquo PLoS ONE vol 8 no6 Article ID e67497 2013

[71] R Saad M R Rizkallah and R K Aziz ldquoGut Pharmacomicro-biomics the tip of an iceberg of complex interactions betweendrugs and gut-associated microbesrdquo Gut Pathogens vol 4 no1 article 16 2012

[72] E J J Van Velzen J A Westerhuis J P M van Duynhovenet al ldquoMultilevel data analysis of a crossover designed humannutritional intervention studyrdquo Journal of Proteome Researchvol 7 no 10 pp 4483ndash4491 2008

[73] T Okubo N Ishihara H Takahashi et al ldquoEffects of partiallyhydrolyzed guar gum intake on human intestinal microfloraand itsmetabolismrdquoBioscience Biotechnology andBiochemistryvol 58 no 8 pp 1364ndash1369 1994

[74] V Mai H A Katki H Harmsen et al ldquoEffects of a controlleddiet and black tea drinking on the fecalmicroflora compositionand the fecal bile acid profile of human volunteers in a double-blinded ramdomized feeding studyrdquo The Journal of Nutritionvol 134 no 2 pp 473ndash478 2004

[75] J-S Jin M Touyama T Hisada and Y Benno ldquoEffectsof green tea consumption on human fecal microbiota withspecial reference to Bifidobacterium speciesrdquoMicrobiology andImmunology vol 56 no 11 pp 729ndash739 2012

[76] J Yamakoshi S Tokutake M Kikuchi Y Kubota H Konishiand T Mitsuoka ldquoEffect of proantocyanidin -rich extract fromgrape seed on human fecal flora and fecalodorrdquo FASEB Journalvol 15 no 4 p A633 2001

[77] X Tzounis A Rodriguez-Mateos J Vulevic G R Gibson CKwik-Uribe and J P E Spencer ldquoPrebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomizedcontrolled double-blind crossover intervention studyrdquo TheAmerican Journal of Clinical Nutrition vol 93 no 1 pp 62ndash722011

[78] M I Queipo-Ortuno M Boto-Ordonez M Murri et alldquoInfluence of red wine polyphenols and ethanol on the gutmicrobiota ecology and biochemical biomarkersrdquo AmericanJournal of Clinical Nutrition vol 95 no 6 pp 1323ndash1334 2012

[79] K Shinohara Y Ohashi K Kawasumi A Terada and TFujisawa ldquoEffect of apple intake on fecal microbiota andmetabolites in humansrdquo Anaerobe vol 16 no 5 pp 510ndash5152010

[80] C I R Gill G J Mcdougall S Glidewell et al ldquoProfiling ofphenols in human fecal water after raspberry supplementationrdquoJournal of Agricultural and Food Chemistry vol 58 no 19 pp10389ndash10395 2010

[81] S Vendrame S Guglielmetti P Riso S Arioli D Klimis-Zacasand M Porrini ldquoSix-week consumption of a wild blueberry

BioMed Research International 15

powder drink increases Bifidobacteria in the human gutrdquoJournal of Agricultural and Food Chemistry vol 59 no 24 pp12815ndash12820 2011

[82] S Guglielmetti D Fracassetti V Taverniti et al ldquoDifferentialmodulation of human intestinal Bifidobacterium populationsafter consumption of a wild blueberry (Vaccinium angusti-folium) drinkrdquo Journal of Agricultural and Food Chemistry vol61 no 34 pp 8134ndash8140 2013

[83] T Clavel M Fallani P Lepage et al ldquoIsoflavones and func-tional foods alter the dominant intestinal microbiota in post-menopausal womenrdquo Journal of Nutrition vol 135 no 12 pp2786ndash2792 2005

[84] A Costabile A Klinder F Fava et al ldquoWhole-grain wheatbreakfast cereal has a prebiotic effect on the human gut micro-biota a double-blind placebo-controlled crossover studyrdquoBritish Journal of Nutrition vol 99 no 1 pp 110ndash120 2008

[85] A L Carvalho-Wells K Helmolz C Nodet et al ldquoDetermina-tion of the in vivo prebiotic potential of a maize-based wholegrain breakfast cereal a human feeding studyrdquo British Journalof Nutrition vol 104 no 9 pp 1353ndash1356 2010

[86] A Cuervo L Valdes N Salazar et al ldquoPilot study of diet andmicrobiota interactive associations of fibers and polyphenolswith human intestinal bacteriardquo Journal of Agricultural andFood Chemistry vol 62 no 23 pp 5330ndash5336 2014

[87] M Jaquet I Rochat J Moulin C Cavin and R BibilonildquoImpact of coffee consumption on the gut microbiota a humanvolunteer studyrdquo International Journal of FoodMicrobiology vol130 no 2 pp 117ndash121 2009

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

Volume 2014

Zoology

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Molecular Biology International

GenomicsInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Signal TransductionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Evolutionary BiologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Genetics Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Virolog y

Hindawi Publishing Corporationhttpwwwhindawicom

Nucleic AcidsJournal of

Volume 2014

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Enzyme Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Microbiology

Page 14: Review Article A Survey of Modulation of Gut Microbiota by ...downloads.hindawi.com/journals/bmri/2015/850902.pdf · Review Article A Survey of Modulation of Gut Microbiota by Dietary

14 BioMed Research International

[53] E Barroso F Sanchez-Patan P J Martın-Alvarez et al ldquoLacto-bacillus plantarum IFPL935 favors the initial metabolism of redwine polyphenols when added to a colonic microbiotardquo Journalof Agricultural and Food Chemistry vol 61 no 42 pp 10163ndash10172 2013

[54] G R Gibson J H Cummings and G T Macfarlane ldquoUse ofa three-stage continuous culture system to study the effect ofmucin on dissimilatory sulfate reduction and methanogenesisby mixed populations of human gut bacteriardquo Applied andEnvironmentalMicrobiology vol 54 no 11 pp 2750ndash2755 1988

[55] KMollyMVandeWoestyne andWVerstraete ldquoDevelopmentof a 5-step multi-chamber reactor as a simulation of thehuman intestinal microbial ecosystemrdquo Applied Microbiologyand Biotechnology vol 39 no 2 pp 254ndash258 1993

[56] M Minekus M Smeets-Peeters A Bernalier et al ldquoAcomputer-controlled system to simulate conditions of thelarge intestine with peristaltic mixing water absorption andabsorption of fermentation productsrdquoAppliedMicrobiology andBiotechnology vol 53 no 1 pp 108ndash114 1999

[57] PDeBoever BDeplancke andWVerstraete ldquoFermentation bygut microbiota cultured in a simulator of the human intestinalmicrobial ecosystem is improved by supplementing a soygermpowderrdquo Journal of Nutrition vol 130 no 10 pp 2599ndash26062000

[58] C S Yang X Wang G Lu and S C Picinich ldquoCancerprevention by tea animal studies molecular mechanisms andhuman relevancerdquoNature Reviews Cancer vol 9 no 6 pp 429ndash439 2009

[59] R E Ley F Backhed P Turnbaugh C A Lozupone R DKnight and J I Gordon ldquoObesity alters gut microbial ecologyrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 102 no 31 pp 11070ndash11075 2005

[60] H Hara N Orita S Hatano et al ldquoEffect of tea polyphenols onfecal flora and fecal metabolic products of pigsrdquo The Journal ofVeterinary Medical Science vol 57 no 1 pp 45ndash49 1995

[61] N Ishihara D-C Chu S Akachi and L R Juneja ldquoImprove-ment of intestinal microflora balance and prevention of diges-tive and respiratory organ diseases in calves by green teaextractsrdquo Livestock Production Science vol 68 no 2-3 pp 217ndash229 2001

[62] P Dolara C Luceri C De Filippo et al ldquoRed wine polyphenolsinfluence carcinogenesis intestinal microflora oxidative dam-age and gene expression profiles of colonicmucosa in F344 ratsrdquoMutation Research-Fundamental and Molecular Mechanisms ofMutagenesis vol 591 no 1-2 pp 237ndash246 2005

[63] S Sembries G Dongowski K Mehrlander F Will and HDietrich ldquoPhysiological effects of extraction juices from applegrape and red beet pomaces in ratsrdquo Journal of Agricultural andFood Chemistry vol 54 no 26 pp 10269ndash10280 2006

[64] S Sembries G Dongowski G Jacobasch K Mehrlander FWill andH Dietrich ldquoEffects of dietary fibre-rich juice colloidsfrom apple pomace extraction juices on intestinal fermentationproducts and microbiota in ratsrdquo British Journal of Nutritionvol 90 no 3 pp 607ndash615 2003

[65] A Viveros S Chamorro M Pizarro I Arija C Centeno andA Brenes ldquoEffects of dietary polyphenol-rich grape productson intestinal microflora and gut morphology in broiler chicksrdquoPoultry Science vol 90 no 3 pp 566ndash578 2011

[66] A H Smith and R I Mackie ldquoEffect of condensed tannins onbacterial diversity andmetabolic activity in the rat gastrointesti-nal tractrdquo Applied and Environmental Microbiology vol 70 no2 pp 1104ndash1115 2004

[67] M Massot-Cladera T Perez-Berezo A Franch M Castelland F J Perez-Cano ldquoCocoa modulatory effect on rat faecalmicrobiota and colonic crosstalkrdquo Archives of Biochemistry andBiophysics vol 527 no 2 pp 105ndash112 2012

[68] M Larrosa M J Yanez-Gascon M V Selma et al ldquoEffectof a low dose of dietary resveratrol on colon microbiotainflammation and tissue damage in a DSS-induced colitis ratmodelrdquo Journal of Agricultural and Food Chemistry vol 57 no6 pp 2211ndash2220 2009

[69] A-L Molan Z Liu andM Kruger ldquoThe ability of blackcurrantextracts to positively modulate key markers of gastrointestinalfunction in ratsrdquoWorld Journal ofMicrobiologyampBiotechnologyvol 26 no 10 pp 1735ndash1743 2010

[70] A Lacombe R W Li D Klimis-Zacas et al ldquoLowbush wildblueberries have the potential to modify gut microbiota andxenobiotic metabolism in the rat colonrdquo PLoS ONE vol 8 no6 Article ID e67497 2013

[71] R Saad M R Rizkallah and R K Aziz ldquoGut Pharmacomicro-biomics the tip of an iceberg of complex interactions betweendrugs and gut-associated microbesrdquo Gut Pathogens vol 4 no1 article 16 2012

[72] E J J Van Velzen J A Westerhuis J P M van Duynhovenet al ldquoMultilevel data analysis of a crossover designed humannutritional intervention studyrdquo Journal of Proteome Researchvol 7 no 10 pp 4483ndash4491 2008

[73] T Okubo N Ishihara H Takahashi et al ldquoEffects of partiallyhydrolyzed guar gum intake on human intestinal microfloraand itsmetabolismrdquoBioscience Biotechnology andBiochemistryvol 58 no 8 pp 1364ndash1369 1994

[74] V Mai H A Katki H Harmsen et al ldquoEffects of a controlleddiet and black tea drinking on the fecalmicroflora compositionand the fecal bile acid profile of human volunteers in a double-blinded ramdomized feeding studyrdquo The Journal of Nutritionvol 134 no 2 pp 473ndash478 2004

[75] J-S Jin M Touyama T Hisada and Y Benno ldquoEffectsof green tea consumption on human fecal microbiota withspecial reference to Bifidobacterium speciesrdquoMicrobiology andImmunology vol 56 no 11 pp 729ndash739 2012

[76] J Yamakoshi S Tokutake M Kikuchi Y Kubota H Konishiand T Mitsuoka ldquoEffect of proantocyanidin -rich extract fromgrape seed on human fecal flora and fecalodorrdquo FASEB Journalvol 15 no 4 p A633 2001

[77] X Tzounis A Rodriguez-Mateos J Vulevic G R Gibson CKwik-Uribe and J P E Spencer ldquoPrebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomizedcontrolled double-blind crossover intervention studyrdquo TheAmerican Journal of Clinical Nutrition vol 93 no 1 pp 62ndash722011

[78] M I Queipo-Ortuno M Boto-Ordonez M Murri et alldquoInfluence of red wine polyphenols and ethanol on the gutmicrobiota ecology and biochemical biomarkersrdquo AmericanJournal of Clinical Nutrition vol 95 no 6 pp 1323ndash1334 2012

[79] K Shinohara Y Ohashi K Kawasumi A Terada and TFujisawa ldquoEffect of apple intake on fecal microbiota andmetabolites in humansrdquo Anaerobe vol 16 no 5 pp 510ndash5152010

[80] C I R Gill G J Mcdougall S Glidewell et al ldquoProfiling ofphenols in human fecal water after raspberry supplementationrdquoJournal of Agricultural and Food Chemistry vol 58 no 19 pp10389ndash10395 2010

[81] S Vendrame S Guglielmetti P Riso S Arioli D Klimis-Zacasand M Porrini ldquoSix-week consumption of a wild blueberry

BioMed Research International 15

powder drink increases Bifidobacteria in the human gutrdquoJournal of Agricultural and Food Chemistry vol 59 no 24 pp12815ndash12820 2011

[82] S Guglielmetti D Fracassetti V Taverniti et al ldquoDifferentialmodulation of human intestinal Bifidobacterium populationsafter consumption of a wild blueberry (Vaccinium angusti-folium) drinkrdquo Journal of Agricultural and Food Chemistry vol61 no 34 pp 8134ndash8140 2013

[83] T Clavel M Fallani P Lepage et al ldquoIsoflavones and func-tional foods alter the dominant intestinal microbiota in post-menopausal womenrdquo Journal of Nutrition vol 135 no 12 pp2786ndash2792 2005

[84] A Costabile A Klinder F Fava et al ldquoWhole-grain wheatbreakfast cereal has a prebiotic effect on the human gut micro-biota a double-blind placebo-controlled crossover studyrdquoBritish Journal of Nutrition vol 99 no 1 pp 110ndash120 2008

[85] A L Carvalho-Wells K Helmolz C Nodet et al ldquoDetermina-tion of the in vivo prebiotic potential of a maize-based wholegrain breakfast cereal a human feeding studyrdquo British Journalof Nutrition vol 104 no 9 pp 1353ndash1356 2010

[86] A Cuervo L Valdes N Salazar et al ldquoPilot study of diet andmicrobiota interactive associations of fibers and polyphenolswith human intestinal bacteriardquo Journal of Agricultural andFood Chemistry vol 62 no 23 pp 5330ndash5336 2014

[87] M Jaquet I Rochat J Moulin C Cavin and R BibilonildquoImpact of coffee consumption on the gut microbiota a humanvolunteer studyrdquo International Journal of FoodMicrobiology vol130 no 2 pp 117ndash121 2009

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

Volume 2014

Zoology

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Molecular Biology International

GenomicsInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Signal TransductionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Evolutionary BiologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Genetics Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Virolog y

Hindawi Publishing Corporationhttpwwwhindawicom

Nucleic AcidsJournal of

Volume 2014

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Enzyme Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Microbiology

Page 15: Review Article A Survey of Modulation of Gut Microbiota by ...downloads.hindawi.com/journals/bmri/2015/850902.pdf · Review Article A Survey of Modulation of Gut Microbiota by Dietary

BioMed Research International 15

powder drink increases Bifidobacteria in the human gutrdquoJournal of Agricultural and Food Chemistry vol 59 no 24 pp12815ndash12820 2011

[82] S Guglielmetti D Fracassetti V Taverniti et al ldquoDifferentialmodulation of human intestinal Bifidobacterium populationsafter consumption of a wild blueberry (Vaccinium angusti-folium) drinkrdquo Journal of Agricultural and Food Chemistry vol61 no 34 pp 8134ndash8140 2013

[83] T Clavel M Fallani P Lepage et al ldquoIsoflavones and func-tional foods alter the dominant intestinal microbiota in post-menopausal womenrdquo Journal of Nutrition vol 135 no 12 pp2786ndash2792 2005

[84] A Costabile A Klinder F Fava et al ldquoWhole-grain wheatbreakfast cereal has a prebiotic effect on the human gut micro-biota a double-blind placebo-controlled crossover studyrdquoBritish Journal of Nutrition vol 99 no 1 pp 110ndash120 2008

[85] A L Carvalho-Wells K Helmolz C Nodet et al ldquoDetermina-tion of the in vivo prebiotic potential of a maize-based wholegrain breakfast cereal a human feeding studyrdquo British Journalof Nutrition vol 104 no 9 pp 1353ndash1356 2010

[86] A Cuervo L Valdes N Salazar et al ldquoPilot study of diet andmicrobiota interactive associations of fibers and polyphenolswith human intestinal bacteriardquo Journal of Agricultural andFood Chemistry vol 62 no 23 pp 5330ndash5336 2014

[87] M Jaquet I Rochat J Moulin C Cavin and R BibilonildquoImpact of coffee consumption on the gut microbiota a humanvolunteer studyrdquo International Journal of FoodMicrobiology vol130 no 2 pp 117ndash121 2009

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

Volume 2014

Zoology

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Molecular Biology International

GenomicsInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Signal TransductionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Evolutionary BiologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Genetics Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Virolog y

Hindawi Publishing Corporationhttpwwwhindawicom

Nucleic AcidsJournal of

Volume 2014

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Enzyme Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Microbiology

Page 16: Review Article A Survey of Modulation of Gut Microbiota by ...downloads.hindawi.com/journals/bmri/2015/850902.pdf · Review Article A Survey of Modulation of Gut Microbiota by Dietary

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

Volume 2014

Zoology

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Molecular Biology International

GenomicsInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Signal TransductionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Evolutionary BiologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Genetics Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Virolog y

Hindawi Publishing Corporationhttpwwwhindawicom

Nucleic AcidsJournal of

Volume 2014

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Enzyme Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Microbiology