期刊
NATURE MEDICINE
卷 24, 期 7, 页码 1070-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41591-018-0061-3
关键词
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资金
- EU-FP7 FLORINASH [Health-F2-2009-241913]
- Medical Research Council [MR/L01632X/1]
- MRC Intermediate Research Fellowship in Data Science [MR/L01632X/1]
- Agence Nationale de la Recherche [RPV09003BBA, ANR 09-GEN TRANSFLORAP, GAD 08-2_378258]
- Ministry of University (MIUR) Progetti di Ricerca di Interesse Nazionale (PAIN) [2015MPESJS 004]
- Ministry of Health Ricerca Finalizzata [RF-2011-02349921]
- Fondazione Roma call for Non -Communicable Diseases NCD 2014
- Ministry of Health FIS project, CIBERobn Pathophysiology of Obesity and Nutrition and FEDER funds [15/01934]
- EU METACARDIS [HEALTH -F4-2012-305312]
- Neuron II [291840]
- MRC [MR/M501797/1]
- Imperial College National Institute of Biomedical Research
- Clinical Phenotyping Centre
- Medical Research Council [MR/M501797/1, MR/L01632X/1] Funding Source: researchfish
- MRC [MR/M501797/1, MR/L01632X/1] Funding Source: UKRI
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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