The Gut Microbiome:

Our Misunderstood

Friend and Foe

Dr Jean-Michel Antoine

Impact of the Gut Microbiome

on Nutrients and non-Nutrients Metabolism

and Energy Availability.

With the Functional Food,

& the Obesity Diabetes

Task forces’ support.

Exploring the Role of the Major Gut Microbiota Clusters on Nutritional and Functional Benefits of Nutrients and Non-Nutrients

Efficacy Markers of Diabetes Risk Gestational Diabetes and Diet Establishment of the Efficacy of Intervention in those with the Metabolic Syndrome

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Grigori Raspoutine

Concept of super-organism:

Joshua Lederberg (1925-2008)

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Infectious history. Lederberg J. Science. 2000;288(5464):287-93

Nobel Prize 1958: transduction

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Gut microbiota - a « new organ… organism? »

UNLIKE THE HUMAN GENOME SEQUENCE, WHICH WE CAN’T CHANGE,

OUR MICROBIOTA CAN BE ALTERED.

10 TIMES MORE CELLS

THAN OUR BODY CELLS

100 TIMES MORE GENES

THAN OUR BODY CELLS

HUMAN

The complex web of gut microbiota contributions to host physiology.

Sekirov I et al. Physiol Rev 2010;90:859-904

©2010 by American Physiological Society

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A new organ with many functions

Gut Physiology: Mucosa, Gases, Nervous system

Barrier

Bio-availabilities of Nutrients, Drugs, Phytochemicals

Immune Systems Inflammation

Homeostasis Perturbation Disease Health

Energy, Fermentations

Brain functions, Behavior Well-

being Comfort

Diarrhea, Infections, IBD Functional disorders, Discomfort, Nafld, Nash, Metabolic Syndrome, Obesity, Diabetes

Entero-hepatic circulation

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Food

Tissues

Commensal Bacteria:

Eating at the same plate

• Eating the same part ?

• Same place ?

• Same time ?

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• NOT the effect of DIETS on microbiota:

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Systematic review of the effects

of the gastro-intestinal microbiota

on selected nutrients

and non-nutrients

Gut microbiota functions

Metabolism of nutrients and other

food components (Panel 2)

• Colette Short (Johnson & Johnson)

• Oliver Hasselwander (DuPont)

• Alexandra Meynier (Mondelez)

• Arjen Nauta (Royal Friesland Campina)

• Peter Putz (Ilsi Europe)

• Ian Rowland (University of Reading)

• Jonathan Swan (University of Reading)

• Jessica Türck (Yakult Europe)

• Joan Vermeiren (Cargill)

• Jean-Michel Antoine (Danone)

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Co-authors of Panel 1

Methodologies: Prospero

• PubMed review

English

March 2005-2015

• Selected Key words on

- Nutrients non-nutrients

- Metabolism

- Gut microbiota

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Nutrients + Energy:

• Dietary Proteins (83 hits)

• Dietary Fats (63 hits)

• Dietary Carbohydrates (41 hits)

• Resistant Starch OR non-digestible starch (31 hits)

• Dietary Fibre (125 hits)

• Daidzein OR soy protein, equol (49 hits)

• Polyphenols OR phenolic acid*, flavonoid*, stilbene*,

tannin*, lignan*, alkylresorcinol*, catechin*, anthocyanin*,

quercetin* (181 hits)

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Metabolism OR

• Breakdown,

• Degradation,

• Fermentation,

• Digestion,

• Transformation,

• Bioavailability,

• Absorption.

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Microbiota OR

• Bacteria

• Flora,

• Microbiome.

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A scientific review by two persons

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Records identified through database searching

(n = 730 )

Records screened (n = 730 )

Records excluded (n = 533 )

Selection:

Eligibility of articles

Energy: 50

Carbohydrates: 16

Protein: 17

Fat: 9

Fibres: 43

Resistant starch: 7

Polyphenols (incl. Daidzein): 52

Excluded articles

Energy: 18

Carbohydrates: 6

Protein: 11

Fat: 4

Fibres: 18

Resistant starch: 0

Polyphenols: 26

Selection:

Eligibility of articles

Energy: 50

Carbohydrates: 16

Protein: 17

Fat: 9

Fibres: 43

Resistant starch: 7

Polyphenols (incl. Daidzein): 52

Studies included

Energy: 32

Carbohydrates: 10

Protein: 6

Fat: 5

Fibres: 25

Resistant starch: 7

Polyphenols (incl. Daidzein): 26

Main reasons for exclusion

• Non human data: Rumen

• In vitro experiment

• Review

• Age below 15 years

• Impact of Diet on Microbiota

• « Imprecise » Microbiota

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Methodology of reading: Energy

• The same substrate is provided and

depending on the microbiota composition:

• Disappearance data or Stool content

Is there the same energy content in stool?

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Disapearance data

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Energy in

Energy out

Methodology of reading: Energy

• The same substrate is provided and

depending on the microbiota composition:

• Disappearance data or Stool content

Is there the same energy content in stool?

• Amount of Metabolites in Stool:

Is there the same amount of each SCFA?,

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Amount of Metabolites

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Energy in

SCFA Butyrate Acetate

Propionate Out

Methodology of reading: Energy

• The same substrate is provided and

depending on the microbiota composition:

• Disappearance data or Stool content

Is there the same energy content in stool?

• Amount of Metabolites in Stool:

Is there the same amount of each SCFA?,

• Metabolic consequences: Weight,

Is there the same weight after the diet?

• In Human , then in Animals

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Consequences: metabolic or others

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Energy in

Results

• Few studies are focusing on the impact of

gut microbiota on bioavailability of

nutrients and non-nutrients.

• For Proteins and Digestible carbohydrates

no human study matching selection criteria

were retriewed.

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Expression of Results

• Complexity of Gut microbiota.

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Main 5 PHYLA in HUMAN GUT MICROBIOTA

Marchesi J. R. : Adv. Appl. Microbiol. 2010; 72: 43–62 28

Plus Archae-bacteria

Expression of Results

• Complexity of Gut microbiota.

• Different level of precision in identification

Phylum: Firmicutes,

Class: Clostridia,

Family, species, strain…

• Example of Energy

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Firmicutes h

Lacto-

bacillales

Lactobacillus

Leuconostoc

Clostridiales

Clostridium

C. Coccoides h

C. Leptum h

C. Difficile h

C. Perfringens h

C. Cellulosi h

Eubacterium

E. Rectale h

E. Ventrosium h

Clusters

Cluster IV

(diversity) a

Cluster XIV a

Lachno-

spiraceae h

Roseburia R. Intestinalis h

Coprococcus h

Dorea h

Rumino-coccaceae

Ruminococcus

R. Obeum h

R. Bromii h

Oscillospira O.

Guillermondi h

Sporobacter S. Termitidis h

Erysipelotrichi Clostridium C. Ramosum a

Actino-bacteria

Bifido-bacteriales Bifidobacterium a

Fusobacteria Fuso-

bacteriaceae Faecali-

bacterium F. Prausnitzii h

Archeabacteria Methano-

brevibacter M. Smithii a

Bacteroidetes h

Bacteroides a

B. thetaiotao-

micron h

B. Vulgatus h

Prevotellaceae Prevotella h,a

Notes for caption: red boxes indicate increase; blue boxes indicate decrease a, data from animal studies; h, data from human studies; p<0.05 for all observations

Energy

Firmicutes

Veillonellaceae

Megaspherae

Selenomonas

Acidaminococcaceae

acidaminococcus

Lacto-

bacillales

Lactobacillus

Leuconostoc

Clostridiales

Clostridium

C. coccoides

C. leptum

C. difficile

C. perfringens

C. cellulosi

Eubacterium

E. rectale

E. ventrosium

Clusters

Cluster IV (diversity)

Cluster XIV

Lachno-spiraceae

Roseburia R. intestinalis

Coprococcus

Dorea

Rumino-coccaceae

Ruminococcus

R. obeum

R. bromii

Oscillospira O. guillermondi

Sporobacter S. termitidis

Erysipelotrichi

Clostrodium C. ramosum

Actino-bacteria

Bifido-bacteriales

Bifidobacterium

Fusobacteria Fuso-

bacteriaceae Faecali-

bacterium F. prausnitzii

Proteobacteria Desulfovibionaceae B.

wadsworthia

Bacteroidetes

Bacteroides

B. thetaiotaomicron

B. vulgatus

Rikenellaceae A. putredinis

Prevotellaceae Prevotella

Archeabacteria Methano-

brevibacter M. smithii

Proteins

Expression of Results

• Starting from the Substrate ?

• Substrate, Which Microbes, Metabolites.

Energy, B. P. A. F. F. ? Metabolites

Proteins, B. P. A. F. F. ? Metabolites

CHO, B. P. A. F. F. ? Metabolites

Fats, B. P. A. F. F. ? Metabolites

Polyphenols B. P. A. F. F. ? Metabolites

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Expression of Results

• Starting from the Microbe ?

• Bacteroides,

• Proteobacteria which Substrate(s)

• Actinobacteria

• Fusobacteria which Metabolite(s)

• Firmicutes

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My son’s proposal

Microbes – Metabolites – Substrates

B Energy

P Protein

A Metabolites CHO

F Fat

F Polyphenols

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Benefits of this review

• « New » way of thinking

beyond the effect of Diet on Microbiota.

• New perspectives in Nutrition !

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Benefits of this review

• New way of thinking

• Trigger more trials to explore it

• To provide some hypothesis to explain

differences between subjects/trials

• Identification of experts in the field.

• Starting to include the microbial logic: e.g.

sparing effect of CHO on Proteins…

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Limits of this review

• Few human data.

• Lack of harmonisation in methodologies.

• End-results: stools are not colonic biotopes

• Correlation,

• No in vitro confirmation

• Mixture of acute and long term trials

• Exclusion of Impact of Diet on Microbiota:

When a substrate is metabolised by a given

species, this species will grow.

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Other Benefits and Limits ?

• During the working cocktail

• During the discussion groups tomorrow

• New perspectives in Nutrition when Drugs

is already working hard on it!

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Impact of Microbiota on Drugs

• Sulfalazine and Azo-bond

• Digoxine and Eggerthela

• Irinotecan and B glucuronidase

• Chloramphenicol and Nitro reductase

• Nitrobenzodiazepine

• Simastatin, Prednisolone, Ranitidine…

• Arsenic Desulfovibrio desulfuricans

(Raspoutine)

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• Colette Short (Johnson & Johnson)

• Oliver Hasselwander (DuPont)

• Alexandra Meynier (Mondelez)

• Arjen Nauta (Royal Friesland Campina)

• Peter Putz (Ilsi Europe)

• Ian Rowland (University of Reading)

• Jonathan Swan (University of Reading)

• Jessica Türck (Yakult Europe)

• Joan Vermeiren (Cargill)

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Once again THANKS to Co-workers

www.ilsi.eu