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

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.
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https://hal-cnrs.archives-ouvertes.fr/hal-03090150
Contributor : Marc-Emmanuel Dumas Connect in order to contact the contributor
Submitted on : Friday, November 26, 2021 - 12:41:18 PM
Last modification on : Tuesday, January 18, 2022 - 2:26:08 PM

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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, Nature Publishing Group, 2018, 24, pp.1070 - 1080. ⟨10.1038/s41591-018-0061-3⟩. ⟨hal-03090150⟩

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