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Human and preclinical studies of the host-gut microbiome co-metabolite hippurate as a marker and mediator of metabolic health

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Item Type:Article
Title:Human and preclinical studies of the host-gut microbiome co-metabolite hippurate as a marker and mediator of metabolic health
Creators Name:Brial, F. and Chilloux, J. and Nielsen, T. and Vieira-Silva, S. and Falony, G. and Andrikopoulos, P. and Olanipekun, M. and Hoyles, L. and Djouadi, F. and Neves, A.L. and Rodriguez-Martinez, A. and Mouawad, G.I. and Pons, N. and Forslund, S. and Le-Chatelier, E. and Le Lay, A. and Nicholson, J. and Hansen, T. and Hyötyläinen, T. and Clément, K. and Oresic, M. and Bork, P. and Ehrlich, S.D. and Raes, J. and Pedersen, O.B. and Gauguier, D. and Dumas, M.E.
Abstract:OBJECTIVE: Gut microbial products are involved in regulation of host metabolism. In human and experimental studies, we explored the potential role of hippurate, a hepatic phase 2 conjugation product of microbial benzoate, as a marker and mediator of metabolic health. DESIGN: In 271 middle-aged non-diabetic Danish individuals, who were stratified on habitual dietary intake, we applied (1)H-nuclear magnetic resonance (NMR) spectroscopy of urine samples and shotgun-sequencing-based metagenomics of the gut microbiome to explore links between the urine level of hippurate, measures of the gut microbiome, dietary fat and markers of metabolic health. In mechanistic experiments with chronic subcutaneous infusion of hippurate to high-fat-diet-fed obese mice, we tested for causality between hippurate and metabolic phenotypes. RESULTS: In the human study, we showed that urine hippurate positively associates with microbial gene richness and functional modules for microbial benzoate biosynthetic pathways, one of which is less prevalent in the Bacteroides 2 enterotype compared with Ruminococcaceae or Prevotella enterotypes. Through dietary stratification, we identify a subset of study participants consuming a diet rich in saturated fat in which urine hippurate concentration, independently of gene richness, accounts for links with metabolic health. In the high-fat-fed mice experiments, we demonstrate causality through chronic infusion of hippurate (20 nmol/day) resulting in improved glucose tolerance and enhanced insulin secretion. CONCLUSION: Our human and experimental studies show that a high urine hippurate concentration is a general marker of metabolic health, and in the context of obesity induced by high-fat diets, hippurate contributes to metabolic improvements, highlighting its potential as a mediator of metabolic health.
Keywords:Animals, Mice
Source:Gut
ISSN:0017-5749
Publisher:BMJ Publishing Group
Volume:70
Number:11
Page Range:2105-2114
Date:7 October 2021
Official Publication:https://doi.org/10.1136/gutjnl-2020-323314
PubMed:View item in PubMed

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