Human and preclinical studies of the host-gut microbiome co-metabolite hippurate as a marker and mediator of metabolic health
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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, Francois; Chilloux, Julien; Nielsen, Trine; Vieira-Silva, Sara; Falony, Gwen; Andrikopoulos, Petros; Olanipekun, Michael; Hoyles, Lesley; Djouadi, Fatima; Neves, Ana L.; Rodriguez-Martinez, Andrea; Mouawad, Ghiwa Ishac; Pons, Nicolas; Forslund, Sofia; Le-chatelier, Emmanuelle; Le Lay, Aurelie; Nicholson, Jeremy; Hansen, Torben; Hyotylainen, Tuulia; Clement, Karine; Oresic, Matej; Bork, Peer; Ehrlich, Stanislav Dusko; Raes, Jeroen; Pedersen, Oluf Borbye; Gauguier, Dominique; Dumas, Marc-Emmanuel.
In: Gut, Vol. 70, No. 11, 2021, p. 2105-2114.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Human and preclinical studies of the host-gut microbiome co-metabolite hippurate as a marker and mediator of metabolic health
AU - Brial, Francois
AU - Chilloux, Julien
AU - Nielsen, Trine
AU - Vieira-Silva, Sara
AU - Falony, Gwen
AU - Andrikopoulos, Petros
AU - Olanipekun, Michael
AU - Hoyles, Lesley
AU - Djouadi, Fatima
AU - Neves, Ana L.
AU - Rodriguez-Martinez, Andrea
AU - Mouawad, Ghiwa Ishac
AU - Pons, Nicolas
AU - Forslund, Sofia
AU - Le-chatelier, Emmanuelle
AU - Le Lay, Aurelie
AU - Nicholson, Jeremy
AU - Hansen, Torben
AU - Hyotylainen, Tuulia
AU - Clement, Karine
AU - Oresic, Matej
AU - Bork, Peer
AU - Ehrlich, Stanislav Dusko
AU - Raes, Jeroen
AU - Pedersen, Oluf Borbye
AU - Gauguier, Dominique
AU - Dumas, Marc-Emmanuel
PY - 2021
Y1 - 2021
N2 - 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 H-1-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.
AB - 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 H-1-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.
KW - intestinal microbiology
KW - glucose metabolism
KW - obesity
KW - colonic microflora
KW - DIET
KW - IMPACT
KW - DIVERSITY
KW - PHENOTYPE
KW - RICHNESS
KW - REVEALS
KW - CATALOG
KW - GENES
KW - SERUM
KW - RAT
U2 - 10.1136/gutjnl-2020-323314
DO - 10.1136/gutjnl-2020-323314
M3 - Journal article
C2 - 33975870
VL - 70
SP - 2105
EP - 2114
JO - Gut
JF - Gut
SN - 0017-5749
IS - 11
ER -
ID: 283755666