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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