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

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Title: Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women
Authors: Hoyles, L
Fernández-Real, JM
Federici, M
Serino, M
Abbott, J
Charpentier, J
Heymes, C
Latorre Luque, J
Anthony, E
Barton, RH
Chilloux, J
Myridakis, A
Martinez-Gili, L
Moreno-Navarrete, JM
Rayah, F
Azalbert, V
Blasco-Baque, V
Puig, J
Xifra, G
Ricart, W
Tomlinson, C
Woodbridge, M
Cardellini, M
Davato, F
Cardolini, I
Porzio, O
Gentilieschi, P
Lopez, F
Foufelle, F
Butcher, SA
Holmes, E
Nicholson, JK
Postic, C
Burcelin, R
Dumas, ME
Item Type: Journal Article
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.
Issue Date: 1-Jul-2018
Date of Acceptance: 12-Apr-2018
URI: http://hdl.handle.net/10044/1/57852
DOI: https://dx.doi.org/10.1038/s41591-018-0061-3
ISSN: 1078-8956
Publisher: Nature Publishing Group
Start Page: 1080
End Page: 1080
Journal / Book Title: Nature Medicine
Volume: 24
Copyright Statement: © 2018 Springer Nature Limited. All rights reserved.
Sponsor/Funder: Commission of the European Communities
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Funder's Grant Number: 305312
MR/L01632X/1
MR/L01632X/1
MR/M501797/1
Keywords: 11 Medical And Health Sciences
Immunology
Publication Status: Published
Online Publication Date: 2018-06-25
Appears in Collections:Division of Surgery
Information and Communication Technology (ICT)
Central Services
Faculty of Medicine
Faculty of Natural Sciences



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