our misunderstood friend and foe - ilsi...
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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.
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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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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
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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
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Entero-hepatic circulation
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Food
Tissues
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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)
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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)
• Jean-Michel Antoine (Danone)
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Co-authors of Panel 1
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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 )
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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
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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
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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
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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?
• 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
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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?
• 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
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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
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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
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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
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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
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