Towards Microbial Fermentation Metabolites as Biomarkers for Health Benefits of Prebiotics"
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1 Towards Microbial Fermentation Metabolites as Biomarkers for Health Benefits of Prebiotics" Kieran Tuohy for working group on Microbial Metabolism and Fermentation SUPPORTED BY THE ILSI EUROPE PREBIOTICS TASK FORCE
2 Expert group members Prof Kristin Verbeke Chair Targid BE Dr Annick Bernalier INRA FR Prof Alan Boobis Imperial College London UK Prof Christine Edwards University of Glasgow UK Dr Anne Franck Cargill BE Prof. Michiel Kleerebezem Wageningen University NL Dr Gunhild Kozianowski Südzucker/BENEO Group DE Dr. Arjen Nauta FrieslandCampina NL Prof. Jeroen Raes Vrije Universiteit Brussels BE Dr Kieran Tuohy Fondazione Edmund Mach IT Dr Ric van Tol Mead Johnson NL Dr. Alessandro Chiodini ILSI Europe BE (Dr. Tobias Recker ILSI Europe BE)
3 Background The ILSI Europe Prebiotic Task Force identified a particular need to explore available evidence for positive or negative physiological effects of microbial (faecal) metabolites on the host. Aim - Exploring how to define and impact digestive health - Looking at the different gut functions that contribute to a healthy gastrointestinal tract and thereby to overall health
4 Prebiotic definition: A prebiotic is a selectively fermented ingredient that results in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health. (Gibson et al Food Science and Technology Bulletin: Functional Foods 7 (1) 1 19.) Persist until the colon Selective fermentation in the colon
5 5
6 Overview on different metabolites Summarising available evidence a. List of relevant metabolites b. Highlighted metabolites Integrated perspectives (harm+benefit) including: - Pharmacological perspectives - Toxicological perspectives - Nutrition perspectives - Normal ranges c. More holistic approach: Profiles Functional analysis of faecal water (include genotoxicity) Metabolomics Metagenome analysis
7 Colonic Microbial Metabolites
8 Metabolism of SCFA
9 Faecal SCFA concentrations
![Faecal [SCFA]](/docs-images/83/88195554/images/10-1.jpg "depend on age")
10 Faecal [SCFA] depend on age
11 Faecal [SCFA] differ in lean v obese
![Faecal [SCFA] poor biomarker of gut health Increased faecal SCFA excretion due to decreased SCFA uptake?](/docs-images/83/88195554/images/12-1.jpg "MCT transporters expression and apical location is promoted by luminal SCFA Increased faecal SCFA excretion could be due to decreased MCT active uptake in high fat/low")
12 Faecal [SCFA] poor biomarker of gut health Increased faecal SCFA excretion due to decreased SCFA uptake? MCT transporters expression and apical location is promoted by luminal SCFA Increased faecal SCFA excretion could be due to decreased MCT active uptake in high fat/low CHO diets Bile salt CDCA and E. coli EPEC inhibit butyrate uptake
13 Little difference in SCFA production in vitro between lean and obese microbiota
14 Faecal [SCFA] in disease states
15 SCFA may beneficially impact on the following mammalian processes Apoptosis Cellular proliferation in non-cancer cells Inflammation Recruitment of immune cells to intestine Neutraphil activity/oxidative burst Adipose tissue adipokine production, fat storage Tight junction control Expression of incretins/gut peptides, and regulation of food intake Intestinal motility Cholesterol production/lipogenesis Glucogenesis Cellular energy metabolism Thermogenesis Inhibits tumorigenesis DNA miss-match repair Note: most mechanistic data from in vitro or animal studies rodents, pigs, chickens
16 Faecal minor organic acids
17 Metabolites of protein fermentation
18 Urinary and faecal levels of p-cresol
19 Urinary and faecal levels of phenol
20 Effects of phenolic derivatives of protein fermentation Effects on epithelial cells mainly determined using in vitro incubation tests Decreased viability Reduced epithelial barrier function No systemic toxicity in healthy subjects Accumulates in serum in chronic kidney disease - uremic toxin Contributes to endothelial disfunction Very limited data on toxicity of indole
21 Faecal [ammonia]
22 Effects of intestinal ammonia Effects on epithelial cells: alters nucleic acid synthesis changes the morphology and intermediary metabolism of intestinal cells reduces the lifespan of cells No adverse effects upon oral admintration Hepatic encephalopathy
23
24 Possible solution A more holistic approach
25 25
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29 Tools for stools!
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32 Thank you! Acknowledgements Prebiotic Task Force, ILSI Europe
Towards Microbial Fermentation Metabolites as Biomarkers for Health Benefits of Prebiotics
Towards Microbial Fermentation Metabolites as Biomarkers for Health Benefits of Prebiotics Kristin Verbeke for working group on Microbial Metabolism and Fermentation SUPPORTED BY THE ILSI EUROPE PREBIOTICS
Towards Microbial Fermentation Metabolites as Biomarkers for Health Benefits of Prebiotics
Towards Microbial Fermentation Metabolites as Biomarkers for Health Benefits of Prebiotics Kristin Verbeke for working group on Microbial Metabolism and Fermentation SUPPORTED BY THE ILSI EUROPE PREBIOTICS
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