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RELACIÓN ENTRE LA MICROBIOTA

INTESTINAL Y LA SALUD Y

CONTRIBUCIÓN DE LA FIBRA EN LA DIETA

Laboratorio de Ecología Microbiana, Nutrición y Salud.

MARINA ROMANÍ-PÉREZ

Laboratorio de Ecología Microbiana, Nutrición y Salud.


OVERVIEW

GUT MICROBIOTA

GUT MICROBIOTA & DISEASES. OBESITY

MICROBIOME-BASED INTERVENTIONS FOR PROMOTING METABOLIC HEALTH.

PREBIOTICS & PROBIOTICS

GUT MICROBIOTA-HOST COMMUNICATION

GROUP OF MICROBIAL ECOLOGY, NUTRITION AND HEALTH.

‘On the way to evaluate new probiotics’

Evaluation of the potential probiotic Bacteroides uniformis CECT 7771

Evaluation of dietary fiber supplementation (WBE) combine with

B. uniformis CECT 7771 intervention

MICROBIOTA-BY-DIET INTERACTION. SCFAs

1

2

3

4

5

6

6.1

6.2

39 trillion

microbial cells

1-3% of body

mass

10 times more

cells than

human cells

150 times more

genes than

human genes

1. GUT MICROBIOTA

Body habitat

groups

HOLOGENOME

HOST GENOME

(Ekaryotic)

GENOME OF SYMBIOTIC

MICROBES (Prokaryotic)

PHENOTYPE

PLASTICITY

The Human Microbiome Project Consortium

HOST

SYMBIOSIS

Dynamic microbial

community struture

among individuals

Host

genome

GenderDrugs

Antibiotics Stress Aging Delivery

mode

DIET

HOST PHENOTYPE

PLASTICITY

FirmicutesClostridium, Enterococcus,

Lactobacillus and Ruminococcus

BacteroidetesBacteroides and Prevotella

Actinobacteria

Proteobacteria

PHYLOGENY OF BACTERIAL PHYLA

1. GUT MICROBIOTA

The Human Microbiome Project Consortium

Stability of metabolic

pathways among individuals

Gut microbiota

Nutrients

Shelter

HOST

• Energy harvest

• Protection against pathogens

• Immunomodulation

• Energy metabolic status

Gut microbiota

Firmicutes

Bacteroidetes

Phyla

CH metabolism

Cofactor & Vitamin

biosynthesis

Gut microbiota

1. GUT MICROBIOTA

HOST

SYMBIOSIS

MUTUALISM

COMMENSALISM

PARASITISM

Eubiosis

SYMBIONTS

Dysbiosis

PATHOSYMBIONTS

SYMBIONTS

X

PATHOSYMBIONTS

Immune homeostasisProinflammatory state

Intestinal and extra-inetstinal

Inflammatory DISEASES

DC

M1

M2

T cells

Treg

B cells

Healthy state

1. GUT MICROBIOTA & HOST

Intestinal and extra-intestinal Inflammatory DISEASES

Inflammatory bowel disease

Celiac disease

Cardiovascular diseases

Mental diseases (emotional, cognitive-related diseases; anxiety, depression,

autism, etc)

Metabolic diseases: Diabetes (T1D or T2D), Obesity, metabolic syndorme

Dysbiosis

PATHOSYMBIONTS

SYMBIONTS

Proinflammatory state

CHRONIC

2. GUT MICROBIOTA & DISEASES

worldobesity.org

www.who.int

KEY FACTS OF OBESITY

• ↗prevalence from 1975 (x3)

• In 2016:

• ADULTS: 39% overweight and 13% obese.

• CHILDREN & ADOLESCENTS: 18% overweight or obese

• Obesity ranks fifth in risk of global deaths in the general

population

• ↗ prevalence in low and middle-income countries

• OBESITY IS PREVENTABLE

2. GUT MICROBIOTA & OBESITY

Systemic Insulin

resistance

↗ adiposity

www.who.int Overweight: 25 ≥ BMI ≤ 30

Obesity: BMI ≥ 30

BMI: Kg/m2

(body mass index)

Insulin

resistance

Metabolic comorbidities

T2D, NAFLD, dyslipidaemia,

cardiovascular disease, etc

State of Chronic low-grade of

inflammation

METABOLIC

PROFILE

X

EnergyintakeEnergy

expenditureEnergy expenditure

Energy intake

Energy imbalance


PATHOPHYSIOLOGY OF OBESITY

adiposity

Glucose intolerance

Over-eating

Insulin resistance

ENERGY IMBALANCE

Brain

Hypothalamus

Gut-brain-periphery axis

Gut

DIET:

Energy-dense foods

Gut microbiota

Periphery

↘ satiety signals sensitivity

ENERGY BALANCE

Restoration of gut-brain

communication

Anti-obesity

interventions

Genetic

factors30-40%

70-60%

Environmental factors

Sedentary

life style

EUBIOSIS


+/+

ob/ob

GF

ob/ob

Donor Metabolic

phenotype

Microbiota

transfer

non-digerible

polysacharides

Energy storage

Individual predisposition to obesity

Gut microbial communities

Extraction and storage of

energy from diet

Gut microbiota is an

enviromental factor of obesity

DIET


Ln

Bacteroidetes

invasion

Cohousing

Ln Ob

Discordant Twins

LeanGF mice

Ln

GF mice

Obese

Ob

Microbiota invasion depends on

microbiota-by-diet

interaction

LoSF-HiFV HiSF-LoFV

Gut microbiota invasion

linked to leaness

x


Manipulation of microbial

community structure

FirmicutesClostridium, Enterococcus,

Lactobacillus and Ruminococcus

BacteroidetesBacteroides and Prevotella

Actinobacteria

Proteobacteria

Obesity

ob/ob 50% fewer Bacteroidetes

Ley et al, Nature 2006

FAT-R, fat restricted

CARB-R, carbohydrate restricted

PROBIOTICS

PREBIOTICS

FECAL TRANSFER

MICROBIOME-BASED

interventions for promoting

metabolic health


3. MICROBIOME-BASED INTERVENTIONS FOR

PROMOTING METABOLIC HEALTH

Romaní-Pérez M et al, 2017

Prebiotics(Food grade component)

Akkermansia

muciniphila

↓ Fat mass

↓ AT inflammation

↑acylglycerols

Improved glucose

homeostasis

GLP-2

↓Inflammation

(↓INFγ)Bacteroides

acidifaciens

Eubacterium

hallii

SCFAs

O=

OH

=

OH

ButyratePropionateAcetate

O=

OH

=

OH

O=

OH

=

OH

EEC: L cells

GLP-1, PYY

↑GLP-1, PYY

FFAR2, FFAR3

Brain

↓ Food intake

?

↑TGR5

↑PPARγ

↓DPPIV

↓ Hepatic TG

SCFAs

?

↑Browning

Secondary

BAs

↑ Thermogenesis

BATTGR5

Mucus layer

Lean healthy

donor

TGR5

OSTα

↑O=

OH

=

OH

O=OH

=

OH

↑ Gut barrier

integrity

Next generation of Probiotics(Live microorganisms)

Microbiota replacement(FMT, microbiota

community transfer)

Microbiome-based

interventions

Alter

composition/activity

of host gut

microbiota

Health benefit

Metabolic Health

NUTRIENT Natural SOURCE

Water-insoluble dietary fibers

Cellulose

Resistant starch

Cereals FruitVegetables

BranCereals Legumes

CerealsGarden beans

Corn Wheat Barley

NUTRIENT Natural SOURCE

Water-soluble dietary fibers

Inulin

Fructooligosaccharides

(FOS)

Arabinoxylan

(Hemicellulose)

Arabinoxylan

oligosaccharides (AXOS)

Pectin

Chicory root

Banana

Onion

Leek

Hemicellulose

Cereals Wheat

Non-starch polysaccharide

(NSP)

bran ~70%endosperm ~88%

Lignin

Fruits Corn

falkes Carrots

3.1 PREBIOTICS

DIETARY FIBER: indigestible plant polysaccharides

Strain

identification

Functional

characterizationSafety

assesment

Efficacy

Phase 2 human trial (DBPC).

Probiotic vs placebo

Effectiveness

Phase 3 human trial

Probiotic vs standard treatment

Probiotic for

FOOD

‘Classical’ probiotics

• Currently commercialized probiotics

• Lactic acid bacteria and bifidobacteria

• Biological samples or derived from fermented foods

Next Generation of

Probiotics (NGP)

Massive use of DNA sequencing in controlled(16S rRNA gene-based approach, whole-genome

shotgun-based approach) epidemiological

studies

NGP: Selected

functionally distinct

indigenous bacteria

with potential higher

efficacy of current

probiotic formulation

Evaluation of the administration

of A. muciniphila on parameters

of Metabolic Syndorme

in vitro & in vivo

3.2 PROBIOTICS

De Filippo et al, PNAS 2010

Burkina Faso childrenDIET: high in FIBER and low in fat

Different diets in human population

European childrenDIET: high in animal PROTEIN, SUGAR and

FAT. Low in fiber

SCFA-producers

Pathogen

intestinal microbes

Benefits to

metabolic health

Xylane, xylose,

carboxymethylcellulose

Whole grains

Dietary fiber

HOST

DIET

Metabolic phenotype

plasticity

Microbial community

structure

MICROBIOTA-BY-DIET INTERACTION

4. MICROBIOTA-BY-DIET INTERACTION. SCFAs

DIETARY FIBER

O=

OH

=

OH

O=

OH

=

OH

O=

OH

=

OH

FERMENTATIONS

Ríos-Covián et al, 2016 & Basson et al, 2016

Bacteroides

Resistant starchs (1, 4),

arabynoxylans, pectin,

inulin, FOS, mucin,

mucopolysaccharides

Gut microbiota

metabolic routes

SHORT CHAIN

FATTY ACIDS

4. MICROBIOTA-BY-DIET INTERACTION. SCFAs

Fiber

Gut hormones.

GLP-1, PYY

EECs: L cells

SCFAs: biactive molecules

O=

OH

=

OHO=

OH

=

OHO=

OH

=

OHGPR41

Gαi

Cellular response

• Enteroendocrine cells

• Neurons

• Inmmune cells

GPR43Gαi

Gαq

O= OH

= OH O =

OH

=

OH

O=

OH

=

OH

Inmune

homeostasis

Energy

homeostasis

COLON

AChColonic

transit

O= OH

= OH O =

OH

=

OH

O=

OH

=

OH

O=

OH

=

OH

O= OH

= OH

O= OH

= OH

5. GUT MICROBIOTA-HOST COMMUNICATION

Adipose tissue

Obesity State of Chronic low-grade of inflammation

increased M1/M2 ratio

IL-6, TNF-α,

IL-1β

LeptinB cells

Cytotoxic T cells

Th1 and Th17

Insulin resistance

Systemic Insulin resistance

DC

M1

M2

T cells

Treg

B cells

MLN

M cellsTLRsNOD

Innate immunitySystemic inflammation

Gut microbiota Intestinal immunity

Gut

permeability

High fat diet

Dysbiosis

High fat diet

LPSDNA

PGN

Metabolic

endotoxemia

Wire et al. Cell Metabolism 2016

IFN-γ

Ab

Adaptative immunity

Inflammatory

mediators

CD4+

MCHI MCHII

CD8+

SCFAs

5. GUT MICROBIOTA-HOST COMMUNICATION

IMMUNOMODULATION

Strain identification

Functional

characterization

Safety

assesment

Phase 2 human trial (DBPC)

Probiotic vs placebo

Phase 3 human trial

Probiotic vs standard treatment

Probiotic for FOOD

in vitro & in vivo

Evaluationof probiotics for food

Pathophysiology of metabolic

and inflammatory diseases

6. GROUP OF MICROBIAL ECOLOGY, NUTRITION AND HEALTH.

‘On the way to evaluate new probiotics’

Bacteroides-Prevotella

Bacteroides fragilis

Anti-obesity effects

• Higher abundance in breast-fed than in

formula-fed infants.

• B. uniformis CECT 7771 isolated

from stools of healthy breast-fed infants

Strain

identification

In vitro Functional

characterization

Gauffin et al. PLoS One. 2012

Macrophages

Different strains

of Bacteroides

6.1 ‘On the way to evaluate new probiotics’

in vitro functional characterization of Bacteroides uniformis CECT 7771

C57BL/6

HFHFD-High Fat High Fructose diet

SD-Standard Diet

Placebo (10% skimmed milk)

B. uniformis CECT 7771 (1X109CFU)


B. uniformis CECT 7771 (1X109CFU)

weeks

PROTEINS

(% of Kcal)

CH

(% of Kcal)

FAT

(% of Kcal)

FRUCTOSE

(% of Kcal)

SD 23 64 13

(corn oil)

0

HFHFD 18 34 48

(palm oil)

20

DIET

10 14

OGTT IMMUNOMETABOLIC

PARAMETERS

IMMUNOMETABOLIC PARAMETERS

Peyer´s

Patches

Blood

Adipose

tissue

Lympoid cells: B cells and T cells

Myeloid cells: macrophages

Cytokines

Triglycerides

Cholesterol

Glucose

Leptin

Emanuel Fabersani

DIET INDUCED OBESITY (DIO)

Fecal

samples

Gut microbiota

In vivo Functional characterization of

Bacteroides uniformis CE T 7771


in vivo functional characterization of Bacteroides uniformis CECT 7771

METABOLIC PHENOTYPE

0

200

400

600

placebo B. uniformis

a

c

b

c

HFHFD

SD

Gly

ce

mia

(m

g/d

L)

0

100

200

300


HFHFD

SD

a

b b b

Ch

ole

ste

rol (m

g/d

L)

0

50

100

150

200


HFHFD

SD

a

b b b

Tri

gly

ce

rid

es (

mg

/dL

)

0

5

10

15


HFHFD

SDa

c c

b

Le

pti

n (

ng

/mL

)

Hyperleptinemia, hyperglycemia, hypercholesterolemia, hypertriglyceridemia

0

15

30

45

60

120

100

200

300

400

500

SD SD+B. uniformis

HFHSD HFHFD+B. uniformis

* **** **

*

time (min)

Gly

ce

mia

(m

g/d

L)

0

10000

20000

30000

40000

50000SD

HFHFDa

b b b


AU

C

Oral glucose intolerance0

2

4

6 SD

HFHFDa

c

bb


ep

WA

T(g

)/1

00

g B

wAdipose tissue

0

20

40

60 SD

HFHFD


a

b bb

% o

f B

od

y w

eig

ht

ga

in

Lean phenotype

Obese phenotype

PROTEINS

(% of Kcal)

CH

(% of Kcal)

FAT

(% of Kcal)

FRUCTOSE

(% of Kcal)

SD 23 64 13

(corn oil)

0

HFHFD 18 34 48

(palm oil)

20

DIET

PROTEINS

(% of Kcal)

CH

(% of Kcal)

FAT

(% of Kcal)

FRUCTOSE

(% of Kcal)

SD 23 64 13

(corn oil)

0

HFHFD 18 34 48

(palm oil)

20

DIET



Mechanistic understanding of how B. uniformis promote anti-obesity effectsAdipose tissue

Peyer´s Patches

MLN

Dendritic cells (DC)Cytotoxic T cell (cyt T) regulatory T cells (Treg)

Cyt T

DC

M1/M2

balance

B cellsTreg

Blood

0

1

2

3

4


HFHFD

SDa

b bbM

1/M

2

0.0

0.5

1.0

1.5

2.0


HFHFD

SDa

c c

b

M1/M

2

0

2

4

6

8

10


HFHFD

SD

a

b

b

b

Tre

g c

ells (

%)

0

5

10

15

20

25


HFHFD

SD

a

b b b

Tre

g c

ells (

%)

0

5

10

15


HFHFD

SD

a

b b,c

c

Tre

g c

ells (

%)

Lean phenotype

Obese phenotype

0

2

4

6

8


HFHFD

SDa

b bb

B c

ells (

%)

0

2

4

6


HFHFD

SDa

bb

c

B c

ells (

%)

0

20

40

60

80


HFHFD

SDa

bb

b

B c

ells (

%)

0.0

0.1

0.2

0.3

0.4

0.5


HFHFD

SD

a

b bb

cyt

oto

xic

T /H

elp

er

T

0.0

0.5

1.0

1.5


HFHFD

SD

a

b bb

cyt

oto

xic

T /H

elp

er

T

0

2

4

6


HFHFD

SD

a

cb,c b

cyt

oto

xic

T /H

elp

er

T

PROTEINS

(% of Kcal)

CH

(% of Kcal)

FAT

(% of Kcal)

FRUCTOSE

(% of Kcal)

SD 23 64 13

(corn oil)

0

HFHFD 18 34 48

(palm oil)

20

DIET

PROTEINS

(% of Kcal)

CH

(% of Kcal)

FAT

(% of Kcal)

FRUCTOSE

(% of Kcal)

SD 23 64 13

(corn oil)

0

HFHFD 18 34 48

(palm oil)

20

DIET

PROINFLAMMATORY STATE

ANTIINFLAMMATORY RESPONSE



Peyer´s Patches

EpWATblood

MLN

Cyt T

DC

M1/M2

balance

B cellsTreg

0

20

40

60

80


HFHFD

SDa

bb

b

B c

ells (

%)

0

20

40

60

80


HFHFD

SDa

bb

b

B c

ells (

%)

0

20

40

60

80


HFHFD

SDa

bb

b

B c

ells (

%)

Lean phenotype

Obese phenotype

0

1000

2000

3000

4000

5000


IFN

***

*

###

*

pg

/g o

f ti

ss

ue

0

10000

20000

30000


IFN

***

**##

pg

/g o

f ti

ss

ue

PROTEINS

(% of Kcal)

CH

(% of Kcal)

FAT

(% of Kcal)

FRUCTOSE

(% of Kcal)

SD 23 64 13

(corn oil)

0

HFHFD 18 34 48

(palm oil)

20

DIET

0

500

1000

1500

2000

2500


TNF

***

** **###p

g/m

L

0

1000

2000

3000


IL-1

***

*

###

***pg

/mL

0

20

40

60

80

100


IL-6

***

*

###

***pg

/mL

0

200

400

600

800


IFN

***

** **##

pg

/mL

PROINFLAMMATORY STATE

ANTIINFLAMMATORY STATE

0

10

20

30

40


IL-33

***

###

pg

/g o

f ti

ss

ue

0

5000

10000

15000


IL-33

***

###

pg

/g o

f ti

ss

ue

0

2000

4000

6000


IL-10

***

###

pg

/g o

f ti

ss

ue

0

20000

40000

60000

80000


IL-10

***

* ###

*

pg

/g o

f ti

ss

ue

0

50

100

150


IL-10

***

****###

pg

/mL

PROTEINS

(% of Kcal)

CH

(% of Kcal)

FAT

(% of Kcal)

FRUCTOSE

(% of Kcal)

SD 23 64 13

(corn oil)

0

HFHFD 18 34 48

(palm oil)

20

DIET



TLRs

Peyer´s Patchesileum


Adipose tissue

Lean phenotype

Obese phenotype

TLR5

PROTEINS

(% of Kcal)

CH

(% of Kcal)

FAT

(% of Kcal)

FRUCTOSE

(% of Kcal)

SD 23 64 13

(corn oil)

0

HFHFD 18 34 48

(palm oil)

20

DIET

TLR2

TLR4

TLR5




0

20

40

60

80


HFHFD

SDa

bb

b

B c

ells (

%)

PROTEINS

(% of Kcal)

CH

(% of Kcal)

FAT

(% of Kcal)

FRUCTOSE

(% of Kcal)

SD 23 64 13

(corn oil)

0

HFHFD 18 34 48

(palm oil)

20

DIET



ALPHA DIVERSITY

Gut microbiota

BETA DIVERSITY

SD

SD+BHFHFD

HFHFD+B

No

rma

lize

dre

ad

co

un

ts

Genera



T5KO mice metabolic sindromeVijay-Kumar et al. 2010

PROTEINS

(% of Kcal)

CH

(% of Kcal)

FAT

(% of Kcal)

FRUCTOSE

(% of Kcal)

SD 23 64 13

(corn oil)

0

HFHFD 18 34 48

(palm oil)

20

DIET

HFHFD

Peyer´s Patches

Adipose tissue

B. uniformis

CECT 7771

O=

OH

=

OH

?Butyrate

BacteroidesLPS

Helicobacter

DC

M1

M2

T cells

Treg

B cells

TLR5

TLR4

TLR2

M1/M2

IFN-γ

Pro-inflamamtory state Insulin resistance obese-like phenotype

IL-33

IL-10

IL-10

M1/M2

IFN-γ

IL-10

IL-33

Summary

TNF-α

IL-6

IL-1α

Anti-inflammatory effects Insulin sensitivity lean-like phenotype

TLR5?



Fernández-Murga & Sanz, PlosOne 2015

• Normal general health status: activity and behavior

• No difference in body weight gain or loss

• No bacterial translocation (blood, liver or mesenteric lymph nodes)

Normal kidney function Normal liver function

Normal pancreatic

functionNormal Gut mucosa integrity

Normal gut integrity

Immunosupression reduced:

-globet cells and villus height/crypt depth ratio in

jejunum.

-crypt width in the colon.

-B. uniformis CECT 7771 reversed the reduced

height/crypt depth ratio in jejunum

Antiinflammatory response

B. uniformis CECT 7771 reduced pro-inflammatory cytokines

B. uniformis CECT 7771 restored inflammatory cytokines of

immunosuppressed mice

Ongoing experiment

Chronic toxicity assay: 3 months

Placebo

2x10^9 CFU

Immunocompetent mice

Immunosuppressed mice

Dose: 100 times

higher than in humans

Acute toxicity

assay: 6 days

Safety assesment


in vivo safety assesment of Bacteroides uniformis CECT 7771

Functional characterizationPrebiotic & Probiotic

intervention for FOODin vitro

Anti-obesity strategies in vivo

in vitro characterization of the dietary patterns and metabolic phenotypes of B. uniformis CECT 7771

Carbon source

(0.5% w/v)

Glucose

inulin

Wheat Bran Extract

(WBE)

gum arabic

pectin

type II mucin

Bacteroides spp:

glycan enriched environments

B. uniformis CECT 7771

Growth fitness of B. uniformis CECT 7771 in

different dietary fibers

Growth phenotypes

0

0,2

0,4

0,6

0,8

0 2 4 6 8 10

Op

tic

al D

en

sit

y (6

00

nm

)

Time (hours)

Doubling time in the log phase

0

20

40

60

80

100

120

140

Do

ub

lin

g tim

e (m

ins

)

Glucose

Gum arabic

WBE

Inulin

Mucin

Pectin

**

WBE

↗non-digestible carbohydrates:

Arabinoxylans

arabinoxylan-degrading

enzymes

Arabinoxylan oligosaccharides

(AXOS)

SCFA

(propionate)Metabolic

health


in vitro functional characterization of WBE and B. uniformis CECT 7771 intervention

Functional characterizationPrebiotic & Probiotic

intervention for FOODin vitro

Anti-obesity strategiesin vivo

in vivo functional characterization on metabolic phenotype of WBE+B. uniformis CECT 7771 intervention



B. uniformis CECT 7771 (1X107 CFU)

weeks1714

OGTT IMMUNOMETABOLIC

PARAMETERS


B. uniformis CECT 7771 (1X107 CFU)

DIET INDUCED OBESITY (DIO)

Kcal (%) PROTEINS CH SUCROSE FAT WHEAT BRAN EXTRACT

Control 20 70 0 10 0

HFHS 20 35 20 45 0

HFHS+F 20 35 20 45 5

WHEAT BRAN

EXTRACTFATSUCROSECHPROTEINSKcal (%)

Kcal (%) Proteins CH Sucrose Fat WBE

SD 20 70 0 10 0

HFHS 20 35 20 45 0

HFHS+WBE 20 35 20 45 5

HFHS-High Fat High Sucrose diet

SD-Standard Diet

HFHS+WBE-HFHS+WBE

C57BL/6


in vivo functional characterization of WBE and B. uniformis CECT 7771 intervention

0 1 2 3 4 5 6 7 8 9

10

11

12

13

14

15

16

17

20

25

30

35

40

45

SD-Vehicle HFHS+WBE

HFHS HFHS+WBE B. uniformis

***

*** *** *** ******

*** *** *****

*

*****

******

*** ***

*** **

***

HFHS B. uniformis

week

Bo

dy w

eig

ht

(g)

0 1 2 3 4 5 6 7 8 9

10

11

12

13

14

15

16

17

20

25

30

35

40

45

SD-Vehicle HFHS+WBE

HFHS HFHS+WBE B. uniformis

***

*** *** *** ******

*** *** *****

*

*****

******

*** ***

*** **

***

HFHS B. uniformis

week

Bo

dy w

eig

ht

(g)

0

10000

20000

30000

40000

50000 *** at least p<0.05*

SD

HFHS

HFHS+WBE


AU

C

0

10000

20000

30000

40000

50000 *** at least p<0.05*

SD

HFHS

HFHS+WBE


AU

C

0

2

4

6

at least p<0.01

p=0.08

SD

HFHS

HFHS+WBE


ep

WA

T(g

)/1

00

g B

w



0

5

10

15

20


HFHS

HFHS+WBE

SD

p at least <0.05

*

Bo

dy w

eig

ht

ga

in (

g)

0

5

10

15

20


HFHS

HFHS+WBE

SD

p at least <0.05

*

Bo

dy w

eig

ht

ga

in (

g)

Preliminary results

Time (min) 0

Oral Glucose(20g/Kg)

15 30 60 120

C57BL/6

Glycemia

OGTT

0

15

30

60

12

0

100

200

300

400

500

SD

HFHS+WBE

HFHS

HFHS+WBE B. uniformis

***

*

******

**

HFHS B. uniformis

week

Gly

ce

mia

(m

g/d

L)

0

15

30

60

12

0

100

200

300

400

500

SD

HFHS+WBE

HFHS

HFHS+WBE B. uniformis

***

*

******

**

HFHS B. uniformis

week

Gly

ce

mia

(m

g/d

L)

min



ONGOING EXPERIMENTS

IMMUNOMETABOLIC PARAMETERS

Blood

Fecal

samplesGut microbiota

composition

WAT

Lympoid cells: B cells, T cells, IEL

Myeloid cells: macrophages, ILCs

Cytokines

Lamina

propria

Epithelium

Liver

BAT

Triglycerides

Cholesterol

Glucose

Leptin

Insulin

Gut hormones

Hypothalamus

WAT

Liver

BAT

Duodenum

Ileum

Colon

SCFA receptors

Hypotalamic

neuropeptides

Energy

metabolism

ENERGY HOMEOSTASIS IMMUNE HOMEOSTASIS


THANK YOU FOR YOUR

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