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

Brial, François (författare)
UMRS 1124 INSERM, Université de Paris Descartes, Paris, France
Chilloux, Julien (författare)
Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
Nielsen, Trine (författare)
Novo Nordisk Foundation Centre for Basic Metabolic Research, University of Copenhagen, Kobenhavn, Denmark
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Vieira-Silva, Sara (författare)
Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
Falony, Gwen (författare)
Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
Andrikopoulos, Petros (författare)
Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK; National Heart & Lung Institute, Section of Genomic & Environmental Medicine, Imperial College London, London, UK
Olanipekun, Michael (författare)
Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK; National Heart & Lung Institute, Section of Genomic & Environmental Medicine, Imperial College London, London, UK
Hoyles, Lesley (författare)
Department of Biosciences, Nottingham Trent University, Nottingham, UK
Djouadi, Fatima (författare)
Centre de Recherche des Cordeliers, Université Paris Descartes, Paris, France; Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Paris, France
Neves, Ana L. (författare)
Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
Rodriguez-Martinez, Andrea (författare)
Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
Mouawad, Ghiwa Ishac (författare)
UMRS 1124 INSERM, Université de Paris Descartes, Paris, France
Pons, Nicolas (författare)
Metagenopolis, INRAE, Paris, Île-de-France, France
Forslund, Sofia (författare)
Forslund Lab, Max Delbrück Centrum für Molekulare Medizin Experimental and Clinical Research Center, Berlin, Berlin, Germany
Le-Chatelier, Emmanuelle (författare)
Metagenopolis, INRAE, Paris, Île-de-France, France
Le Lay, Aurélie (författare)
UMRS 1124 INSERM, Université de Paris Descartes, Paris, France
Nicholson, Jeremy (författare)
Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
Hansen, Torben (författare)
Novo Nordisk Foundation Centre for Basic Metabolic Research, University of Copenhagen, Kobenhavn, Denmark
Hyötyläinen, Tuulia, 1971- (författare)
Örebro universitet,Institutionen för naturvetenskap och teknik
Clément, Karine (författare)
INSERM, U1166, team 6 Nutriomique, Université Pierre et Marie Curie-Paris 6, Paris, France; Institute of Cardiometabolism and Nutrition (ICAN), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France
Oresic, Matej, 1967- (författare)
Örebro universitet,Institutionen för medicinska vetenskaper
Bork, Peer (författare)
Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
Ehrlich, Stanislav Dusko (författare)
Metagenopolis, INRAE, Paris, Île-de-France, France; Center for Host Microbiome Interactions, King's College London Dental Institute, London, UK
Raes, Jeroen (författare)
Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium; Center for Microbiology, Vlaams Instituut voor Biotechnologie, Leuven, Belgium
Pedersen, Oluf Borbye (författare)
Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium; Center for Microbiology, Vlaams Instituut voor Biotechnologie, Leuven, Belgium
Gauguier, Dominique (författare)
UMRS 1124 INSERM, Université de Paris Descartes, Paris, France
Dumas, Marc-Emmanuel (författare)
Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK; National Heart & Lung Institute, Section of Genomic & Environmental Medicine, Imperial College London, London, UK; McGill Genome Centre & Department of Human Genetics, McGill University, Montréal, Québec, Canada; European Genomics Institute for Diabetes, INSERM U1283, CNRS UMR8199, Institut Pasteur de Lille, Lille University Hospital, Unversity of Lille, Lille, France
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 (creator_code:org_t)
BMJ Publishing Group Ltd, 2021
2021
Engelska.
Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:11, s. 2105-2114
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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 1H-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.

Ämnesord

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)

Nyckelord

Colonic microflora
glucose metabolism
intestinal microbiology
obesity

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