Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women - Archive ouverte HAL Access content directly
Journal Articles Nature Medicine Year : 2018

Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women

(1) , (2) , (3) , (4) , (1) , (5) , (5) , (2) , (6) , (7) , (1) , (1) , (1) , (2) , (6) , (5) , (5) , (2) , (2) , (2) , (1) , (1) , (8) , (8) , (8) , (8, 9) , (8) , (5) , (10) , (1) , (1) , (1) , (6) , (6) , (1)
1
2
3
4
5
6
7
8
9
10
Lesley Hoyles
Massimo Federici
  • Function : Author
  • PersonId : 1139347
James Abbott
Elodie Anthony
  • Function : Author
Julien Chilloux
Antonis Myridakis
Laura Martinez-Gili
Fadila Benhamed
Christopher Tomlinson
Mark Woodbridge
Sarah A Butcher
Catherine Postic
  • Function : Author
Rémy Burcelin
  • Function : Author
  • PersonId : 862437
Marc-Emmanuel Dumas

Abstract

Hepatic steatosis is a multifactorial condition that is often observed in obese patients and is a prelude to non-alcoholic fatty liver disease. Here, we combine shotgun sequencing of fecal metagenomes with molecular phenomics (hepatic transcriptome and plasma and urine metabolomes) in two well-characterized cohorts of morbidly obese women recruited to the FLORINASH study. We reveal molecular networks linking the gut microbiome and the host phenome to hepatic steatosis. Patients with steatosis have low microbial gene richness and increased genetic potential for the processing of dietary lipids and endotoxin biosynthesis (notably from Proteobacteria), hepatic inflammation and dysregulation of aromatic and branched-chain amino acid metabolism. We demonstrated that fecal microbiota transplants and chronic treatment with phenylacetic acid, a microbial product of aromatic amino acid metabolism, successfully trigger steatosis and branched-chain amino acid metabolism. Molecular phenomic signatures were predictive (area under the curve = 87%) and consistent with the gut microbiome having an effect on the steatosis phenome (>75% shared variation) and, therefore, actionable via microbiome-based therapies.
Fichier principal
Vignette du fichier
emss-77125.pdf (2.9 Mo) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-03090150 , version 1 (26-11-2021)

Identifiers

Cite

Lesley Hoyles, José-Manuel Fernández-Real, Massimo Federici, Matteo Serino, James Abbott, et al.. Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women. Nature Medicine, 2018, 24, pp.1070 - 1080. ⟨10.1038/s41591-018-0061-3⟩. ⟨hal-03090150⟩
31 View
14 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More