Imperial College London
Portrait Picture

Professor Marc-Emmanuel Dumas

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Chair in Systems Medicine
 
 
 
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Contact

 

+44 (0)20 7594 1820m.dumas Website

 
 
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Assistant

 

Mrs Patricia Murphy +44 (0)20 7594 1603

 
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Location

 

E315BBurlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@unpublished{Brial:2019:10.1101/2019.12.15.876672,
author = {Brial, F and Chilloux, J and Nielsen, T and Vieira-Silva, S and Falony, G and Hoyles, L and Neves, A and Rodriguez-Martinez, A and Mouawad, GI and Pons, N and Forslund, S and Chatelier, EL and Le, Lay A and Nicholson, J and Hansen, T and Clément, K and Bork, P and Ehrlich, D and Raes, J and Pedersen, O and Gauguier, D and Dumas, M-E and MetaHIT, consortium},
doi = {10.1101/2019.12.15.876672},
publisher = {Cold Spring Harbor Laboratory},
title = {Microbiome determinants and physiological effects of the benzoate-hippurate microbial-host co-metabolic pathway},
url = {http://dx.doi.org/10.1101/2019.12.15.876672},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - Objective Gut microbial products are involved in type 2 diabetes, obesity and insulin resistance. In particular, hippurate, a hepatic phase 2 conjugation product of microbial benzoate metabolism, has been associated with a healthy phenotype. This study aims to identify metagenomic determinants and test protective effects of hippurate.Design We profiled the urine metabolome by 1H Nuclear Magnetic Resonance (NMR) spectroscopy to derive associations with metagenomic sequences in 271 middle-aged Danish individuals to identify dietary patterns in which urine hippurate levels were associated with health benefits. We follow up with benzoate and hippurate infusion in mice to demonstrate causality on clinical phenotypes.Results In-depth analysis identifies that the urine hippurate concentration is associated with microbial gene richness, microbial functional redundancy as well as functional modules for microbial benzoate biosynthetic pathways across several enterotypes. Through dietary stratification, we identify a subset of study participants consuming a diet rich in saturated fat in which urine hippurate, independently of gene richness, accounts for links with metabolic health that we previously associated with gene richness. We then demonstrate causality in vivo through chronic subcutaneous infusions of hippurate or benzoate (20 nmol/day) resulting in improved glycemic control in mice fed a high-fat diet. Hippurate improved insulin secretion through increased β-cell mass and reduced liver inflammation and fibrosis, whereas benzoate treatment resulted in liver inflammation.Conclusion Our translational study shows that the benzoate-hippurate pathway brings a range of metabolic improvements in the context of high-fat diets, highlighting the potential of hippurate as a mediator of metabolic health.
AU  - Brial,F
AU  - Chilloux,J
AU  - Nielsen,T
AU  - Vieira-Silva,S
AU  - Falony,G
AU  - Hoyles,L
AU  - Neves,A
AU  - Rodriguez-Martinez,A
AU  - Mouawad,GI
AU  - Pons,N
AU  - Forslund,S
AU  - Chatelier,EL
AU  - Le,Lay A
AU  - Nicholson,J
AU  - Hansen,T
AU  - Clément,K
AU  - Bork,P
AU  - Ehrlich,D
AU  - Raes,J
AU  - Pedersen,O
AU  - Gauguier,D
AU  - Dumas,M-E
AU  - MetaHIT,consortium
DO  - 10.1101/2019.12.15.876672
PB  - Cold Spring Harbor Laboratory
PY  - 2019///
TI  - Microbiome determinants and physiological effects of the benzoate-hippurate microbial-host co-metabolic pathway
UR  - http://dx.doi.org/10.1101/2019.12.15.876672
UR  - http://hdl.handle.net/10044/1/87331
ER  -
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