The Gut Microbiome: Our Misunderstood Friend and Foe
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1 The Gut Microbiome: Our Misunderstood Friend and Foe Impact of the Gut Microbiome on Nutrients and non-nutrients Metabolism and Energy Availability. Dr Jean-Michel Antoine
2 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
3 Grigori Raspoutine 3
4 Concept of super-organism: Joshua Lederberg ( ) Nobel Prize 1958: transduction Infectious history. Lederberg J. Science. 2000;288(5464):
5 Gut microbiota - a «new organ organism?» 10 TIMES MORE CELLS THAN OUR BODY CELLS 100 TIMES MORE GENES THAN OUR BODY CELLS HUMAN UNLIKE THE HUMAN GENOME SEQUENCE, WHICH WE CAN T CHANGE, OUR MICROBIOTA CAN BE ALTERED. 5
6 The complex web of gut microbiota contributions to host physiology. Sekirov I et al. Physiol Rev 2010;90: by American Physiological Society 6
7 A new organ with many functions Health Homeostasis Perturbation Disease Bio-availabilities of Nutrients, Drugs, Phytochemicals Wellbeing Comfort Brain functions, Behavior Gut Physiology: Mucosa, Gases, Nervous system Barrier Immune Systems Inflammation Energy, Fermentations Diarrhea, Infections, IBD Functional disorders, Discomfort, Nafld, Nash, Metabolic Syndrome, Obesity, Diabetes 7
8 Entero-hepatic circulation Tissues Food 8
9 Commensal Bacteria: Eating at the same plate Eating the same part? Same place? Same time? 9
10 Systematic review of the effects of the gastro-intestinal microbiota on selected nutrients and non-nutrients NOT the effect of DIETS on microbiota: Gut microbiota functions Metabolism of nutrients and other food components (Panel 2) 10
11 Co-authors of Panel 1 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) 11
12 Methodologies: Prospero PubMed review English March Selected Key words on - Nutrients non-nutrients - Metabolism - Gut microbiota 12
13 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) 13
14 Metabolism OR Breakdown, Degradation, Fermentation, Digestion, Transformation, Bioavailability, Absorption. 14
15 Microbiota OR Bacteria Flora, Microbiome. 15
16 A scientific review by two persons Records identified through database searching (n = 730 ) Records screened (n = 730 ) Records excluded (n = 533 ) 16
17 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
18 Selection: Eligibility of articles Studies included Energy: 50 Carbohydrates: 16 Protein: 17 Fat: 9 Fibres: 43 Resistant starch: 7 Polyphenols (incl. Daidzein): 52 Energy: 32 Carbohydrates: 10 Protein: 6 Fat: 5 Fibres: 25 Resistant starch: 7 Polyphenols (incl. Daidzein): 26
19 Main reasons for exclusion Non human data: Rumen In vitro experiment Review Age below 15 years Impact of Diet on Microbiota «Imprecise» Microbiota 19
20 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? 20
21 Disapearance data Energy in Energy out 21
22 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?, 22
23 Amount of Metabolites Energy in SCFA Butyrate Acetate Propionate Out 23
24 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 24
25 Consequences: metabolic or others Energy in 25
26 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. 26
27 Expression of Results Complexity of Gut microbiota. 27
28 Main 5 PHYLA in HUMAN GUT MICROBIOTA Plus Archae-bacteria Marchesi J. R. : Adv. Appl. Microbiol. 2010; 72:
29 Expression of Results Complexity of Gut microbiota. Different level of precision in identification Phylum: Firmicutes, Class: Clostridia, Family, species, strain Example of Energy 29
30 Lacto- bacillales Lactobacillus Leuconostoc Energy C. Coccoides h C. Leptum h Bacteroidetes h Bacteroides a Prevotellaceae B. thetaiotaomicron h B. Vulgatus h Prevotella h,a Clostridium C. Difficile h C. Perfringens h C. Cellulosi h E. Rectale h Eubacterium E. Ventrosium h Firmicutes h Clostridiales Clusters Cluster IV (diversity) a Cluster XIV a Roseburia R. Intestinalis h Actinobacteria Bifidobacteriales Bifidobacterium a Lachnospiraceae h Coprococcus h Fusobacteria Archeabacteria Faecalibacterium Methanobrevibacter Fusobacteriaceae M. Smithii 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 F. Prausnitzii h Ruminococcaceae Dorea h Ruminococcus R. Obeum h R. Bromii h Oscillospira O. Guillermondi h Sporobacter Erysipelotrichi Clostridium C. Ramosum a S. Termitidis h
31 Bacteroides B. thetaiotaomicron Veillonellac eae Acidaminoc occaceae Megaspherae Selenomonas acidaminococcus Proteins Bacteroidetes Rikenellaceae B. vulgatus A. putredinis Lacto- bacillales Lactobacillus Leuconostoc C. coccoides Prevotellaceae Prevotella C. leptum Clostridium C. difficile C. perfringens C. cellulosi E. rectale Firmicutes Eubacterium E. ventrosium Clostridiales Clusters Cluster IV (diversity) Cluster XIV Actinobacteria Bifidobacteriales Bifidobacterium Roseburia R. intestinalis Fusobacteria Fusobacteriaceae Faecalibacterium F. prausnitzii Lachnospiraceae Coprococcus Dorea Proteobacteria Desulfovibionaceae B. wadsworthia Ruminococc us R. obeum R. bromii Ruminococcaceae Oscillospira O. guillermondi Archeabacteria Methanobrevibacter M. smithii Sporobacter S. termitidis Erysipelotri chi Clostrodium C. ramosum
32 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 32
33 Expression of Results Starting from the Microbe? Bacteroides, Proteobacteria Actinobacteria Fusobacteria Firmicutes which Substrate(s) which Metabolite(s) 33
34 My son s proposal Microbes Metabolites Substrates B Energy P Protein A Metabolites CHO F Fat F Polyphenols 34
35 Benefits of this review «New» way of thinking beyond the effect of Diet on Microbiota. New perspectives in Nutrition! 35
36 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 36
37 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. 37
38 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! 38
39 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) 39
40 Once again THANKS to Co-workers 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) 40
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