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.

Hoyles, L., Fernández-Real, J., Federici, M., Serino, M., Abbott, J., Charpentier, J., et al. (2018). Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women. NATURE MEDICINE, 24(7), 1070-1080 [10.1038/s41591-018-0061-3].

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

Federici, Massimo;Cardellini, Marina;Davato, Francesca;Porzio, Ottavia;Gentileschi, Paolo;
2018

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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/18
English
Animals
Cells, Cultured
Cohort Studies
Confounding Factors, Epidemiologic
Diabetes Mellitus
Fecal Microbiota Transplantation
Female
Hepatocytes
Humans
Metabolome
Metabolomics
Mice
Microbiota
Non-alcoholic Fatty Liver Disease
Obesity
Phenotype
Transcriptome
Metagenomics
Hoyles, L., Fernández-Real, J., Federici, M., Serino, M., Abbott, J., Charpentier, J., et al. (2018). Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women. NATURE MEDICINE, 24(7), 1070-1080 [10.1038/s41591-018-0061-3].
Hoyles, L; Fernández-Real, J; Federici, M; Serino, M; Abbott, J; Charpentier, J; Heymes, C; Luque, Jl; Anthony, E; Barton, Rh; Chilloux, J; Myridakis, A; Martinez-Gili, L; Moreno-Navarrete, Jm; Benhamed, F; Azalbert, V; Blasco-Baque, V; Puig, J; Xifra, G; Ricart, W; Tomlinson, C; Woodbridge, M; Cardellini, M; Davato, F; Cardolini, I; Porzio, O; Gentileschi, P; Lopez, F; Foufelle, F; Butcher, Sa; Holmes, E; Nicholson, Jk; Postic, C; Burcelin, R; Dumas, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/306479
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