Post on 15-Aug-2021
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Microbiota y edulcorantes: situación actual
Prof. Angel Gil
Departamento de Bioquímica y Biología Molecular, Instituto de Nutrición y Tecnología de los
Alimentos, Centro de Investigación Biomédica, Universidad de Granada. CIBEROBN, Madrid
Presidente de la Fundación Iberomericana de Nutrición (FINUT)
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Declaración de Intereses: - No tengo ningún interés que declarar en relación a esta presentación
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CTS-461 Nutritional Biochemistry
4 http://www.nature.com/nature/focus/humanmicrobiota/
MICROBIOTA HUMANA
Una compleja comunidad de microorganimos colonizan la piel y las mucosas
5 Bajzer M, Seeley RJ Nature 2006; 444, 1009-1010
MICROBIOTA Y MICROBIOMA INTESTINAL HUMANO
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DISTRIBUCIÓN ESPECÍFICA DE PHYLUM BACTERIANOS EN LOS
HUMANOS SANOS
Les Dethlefsen et al. (2007) Nature 449, 811-818
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VARIACIÓN EN LA COMPOSICIÓN Y EL NÚMERO DEL MICROBIOMA EN
DIFERENTES PARTES DEL INTESTINO HUMANO
Plaza J, Gil A. El microbioma humano. En: Gil A. Tratado de Nutrición, 3ª Ed, Vol II, Ed. Médica Panamericana, Madrid, 2017
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FUNCIONES DE LA MICROBIOTA INTESTINAL
O’Hara AM, Shanahan F, EMBO reports 2006; 7:688- 693
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Kostic AD, et al. Gastroenterology 2014;146:1489–1499
FACTORES QUE AFECTAN LA ESTABILIDAD Y COMPLEJIDAD DEL MICROBIOMA HUMANO
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ALTERACIONES DE LA MICROBIOTA INTESTINAL ASOCIADAS CON VARIAS
ENFERMEDADES
Schroeder & Bäckhed. Nature Med 2016; 22:1079-89
11 David et al. Nature 2014; 5 0 5: 5 5 9-566
MICROBIOTA Y NUTRICIÓN La dieta altera rápidamente la microbiota del intestino humano y su actividad
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CLASIFICACIÓN DE LOS EDULCORANTES
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EDULCORANTES ARTIFICIALES: DIVERSIDAD ESTRUCTURAL
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EDULCORANTES ARTIFICIALES: DIVERSIDAD ESTRUCTURAL
Ruiz-Ojeda et al., Adv Nutr, 2018 ( in press)
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EDULCORANTES Y MICROBIOTA
Suez et al. Nature, 514, 2014
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EDULCORANTES Y MICROBIOTA ¿EFECTOS PERJUDICIALES PARA LA SALUD?
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Synthetic sweeteners Articles Natural sweeteners Articles
Aspartame 8 Neohesperidine Dihydrochalcone 0
Acesulfame 6 Neotame 0
Acesulfame K 4 Stevia 6
Cyclamate 8 Thaumatin 1
Saccharin 16 Glycyrrhizin 6
sucralose 12 Monellin 0
dulcin 0
Articles
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31
2
15
22
0
5
9
0
3
Articles
133
Intensive Sweeteners
Nutritive Sweeteners
Polyols
Sorbitol
Fructooligosaccharides
Xylitol
Isomalt
Mannitol
Hydrogenated starch hydrolysates
Maltitol
Erythritol
Polyglycitol
Arabitol
Advantame
New sugars
Effects of sweeteners on the gut microbiota: a review of experimental and clinical trials
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EDULCORANTES Y MICROBIOTA
Ruiz-Ojeda et al., Adv Nutr, 2018 ( in press)
Sweetener Reference Model Dose Tested Method of microbial
analysis Main outcomes Magnitude of change
Acesulfame K (E-
950)
Pfeffer et al. (22) Rats 3% of acesulfame Inhibitory activity in
cecal content Acesulfame K might act on glucose transport systems Marginally inhibited
Frankenfeld et
al. (23) Human trial 1.7 mg to 33.2 mg/day 16S rRNA
Consumption was not associated with the functional
capability of the gut microbiota
Reduction in bacterial
diversity from 24 to 7 phylum
Uebanso et al.
(24) Mice
15 mg/kg body
weight/day
PCR Denaturing
Gradient Gel
Electrophoresis
Scarce effects on the gut microbiota and its
metabolism Marginal changes
Bian et al. (25) Mice 37.5 mg/kg body
weight/day
16S rRNA and gas
chromatography
The population of Bacteroides was highly increased in
acesulfame K-treated male mice. Conversely, in
female mice, acesulfame K decreased the
Lactobacillus and Clostridium populations
The bacterial genera increase
more than twice
Aspartame (E-
951)
Horwitz et al.
(26) Human trial 400 mg of aspartame
Ingestion and analysis of
area under the curve
Plasma glucose declined and the peak insulin levels
in subjects treated with aspartame, no effects on gut
microbiota
No changes
Tordoff and
Alleva (27) Human trial 590 mg of aspartame
Ingestion and dietary
record
Aspartame reduced sugar intake, no effects on gut
microbiota No changes
Palmnäs et al.
(28) Rats
60 mg/L of drinking
water qRT-PCR analysis
Increased numbers of Enterobacteriaceae and
Clostridium leptum
More than 10 percentage of
increase
Suez et al. (15) Mice 4% of aspartame 16S rRNA No change in the intestinal microbiota No changes
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EDULCORANTES Y MICROBIOTA
Sweetener Reference Model Dose Tested Method of microbial
analysis Main outcomes
Magnitude of
change
Cyclamate
(E-952)
Drasar et
al. (37) Rats
100 mg of calcium
cyclamate 14C- analysis No effects on the gut microbiota No changes
Mallet et
al. (38) In vitro
25 to 75% of
cyclamate
concentration of
medium
Two-stage continuous
culture system No effects on the gut microbiota No changes
Pfeffer et
al. (22) In vitro 5% of cyclamate
Inhibitory activity in
cecal content
Cyclamate decreased glucose
fermentation
Marginally
inhibited
Ruiz-Ojeda et al., Adv Nutr, 2018 ( in press)
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EDULCORANTES Y MICROBIOTA
Sweetener Reference Model Dose Tested Method of microbial
analysis Main outcomes Magnitude of change
Saccharin (E-954)
Anderson et al.
(40) Rats 7.5% of sodium saccharin
Enzymatic activity and
microbiology analyses
Saccharin did not alter the total numbers of
anaerobic microbes but deleted a specific
anaerobic microbe in the cecal contents
Marginally inhibited
Naim et al. (41) Rats 2.5% of sodium saccharin Enzymatic activity and
microbiology analyses
Saccharin inhibited the growth of three
Lactobacillus strains and three E. coli strains
Almost 40% of growth
inhibition
Pfeffer et al. (22) In vitro 0.5% of saccharin Inhibitory activity in cecal
content
Saccharin inhibited glucose fermentation by the
gut microbiota in Cara rats Marginally inhibited
Daly et al. (42) Piglets 0.015% (w/w) of saccharin and
neohesperidin dihydrochalcone 16S rRNA
Neohesperidin dihydrochalcone/saccharin
increased the cecal populations of Lactobacillus
and the intraluminal lactic acid concentration
Increase three times of
lactobacilli population
Daly et al. (43) Piglets 0.015% (w/w) of saccharin and
neohesperidin dihydrochalcone 16S rRNA
Saccharin caused significant shifts in microbial
composition Increase lactobacilli
Suez et al. (15) Mice/Human trial 120 mg of saccharin 16S rRNA
Alterations in metabolic pathways linked with
glucose tolerance and dysbiosis in healthy human
subjects
Difference was 30 percentage
Labrecque et al.
(44) Mice 0.066% (w/v) saccharin in water qRT-PCR analysis
Eubacteria were increased in the pregnant group
that received ethanol plus saccharin and the
presence of saccharin reduces Clostridium levels
Reduction in Clostridium was
almost 50%
Bian et al. (45) Mice 0.3 mg/ml in drinking water 16S rRNA Altered gut bacterial genera, was associated with
the saccharin-induced liver inflammation
Intestinal microbiota changes
were observed in
Ruminococcus
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EDULCORANTES Y MICROBIOTA
Sweetener Reference Model Dose Tested Method of microbial
analysis Main outcomes Magnitude of change
Neotame
(E-961) - - - - No effects on gut microbiota No changes
Advantame
(E-969) - - - - No effects on gut microbiota No changes
Sucralose
(E-955)
Abou-Donia
et al. (47) Rats
100, 300, 500, or
1000 mg/kg
Bacteriological
analyses
The consumption of sucralose
decreases the total anaerobes and
aerobic bacteria, bifidobacteria,
lactobacilli, Bacteroides and
Clostridia
The decrease was more
than two fold
Uebanso et
al. (48) Mice
15 mg/kg body
weight/day
PCR Denaturing
Gradient Gel
Electrophoresis
Sucralose administration
produced modifications in
Clostridium cluster XIVa
The inhibition was more
than 50 %
Ruiz-Ojeda et al., Adv Nutr, 2018 ( in press)
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EDULCORANTES Y MICROBIOTA
Ruiz-Ojeda et al., Unpublished data
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CONCLUSIONES
Los edulcorantes autorizados, evaluados por la FDA, EFSA y Codex
Alimentarius se consideran seguros y bien tolerados.
Los efectos de los edulcorantes sobe la microbiota intestinal no han sido
evaluados de forma completa y apropiada y existen muy pocos estudios
controlados en humanos.
Entre los edulcorantes acalóricos artificiales sólo la sacarina y la sucralosa
parecen influenciar la microbiota intestinal, especialmente cuando se
utilizan dosis elevadas
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CONCLUSIONES
Estudios preliminares indican que la ingesta de sacarina por animales y
humanos se ha asociado a alteraciones en vías metabólicas
relacionadas con la tolerancia a la glucosa y la disbiosis, peor es
necesario realizar estudios controlados para confirmar estas
observaciones
Los edulcorantes de tipo poliol parecen ejercer efectos beneficiosos
sobre la microbiota intestinal, comportándose como verdaderos
probióticos
Entre los edulcorantes naturales sólo los extractos de stevia parecen
modificar ligeramente la composición de la microbiota