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Title: Intestinal Virome Signature Associated With Severity of Nonalcoholic Fatty Liver Disease.

Authors: Lang, Sonja; Demir, Münevver; Martin, Anna; Jiang, Lu; Zhang, Xinlian; Duan, Yi; Gao, Bei; Wisplinghoff, Hilmar; Kasper, Philipp; Roderburg, Christoph; Tacke, Frank; Steffen, Hans-Michael; Goeser, Tobias; Abraldes, Juan G; Tu, Xin M; Loomba, Rohit; Stärkel, Peter; Pride, David; Fouts, Derrick E; Schnabl, Bernd

Published In Gastroenterology, (2020 11)

Abstract: BACKGROUND & AIMS: Alterations in the gut microbiome have been associated with the severity of nonalcoholic fatty liver disease (NAFLD). Previous studies focused exclusively on the bacteria in the microbiome; we investigated changes in the viral microbiome (virome) in patients with NAFLD. METHODS: In a prospective, cross-sectional, observational study, we extracted RNA and DNA virus-like particles from fecal samples from 73 patients with NAFLD: 29 patients had an NAFLD Activity Score (NAS) of 0-4, 44 patients had an NAS of 5-8 or liver cirrhosis (LCI), 37 patients had F0-F1 fibrosis, and 36 patients had F2-F4 fibrosis. As controls, 9 individuals without liver disease and 13 patients with mild primary biliary cholangitis were included in the analysis. We performed shotgun metagenomic sequencing of virus-like particles. RESULTS: Patients with NAFLD and NAS 5-8/LCI had a significant decrease in intestinal viral diversity compared with patients with NAFLD and NAS 0-4 or control individuals. The presence of more advanced NAFLD was associated with a significant reduction in the proportion of bacteriophages compared with other intestinal viruses. Using multivariate logistic regression analysis with leave-1-out cross validation, we developed a model, including a viral diversity index and simple clinical variables, that identified patients with NAS 5-8/LCI with an area under the curve of 0.95 (95% confidence interval, 0.91-0.99) and F2-F4 fibrosis with an area under the curve of 0.88 (95% confidence interval, 0.80-0.95). Addition of data on viral diversity significantly improved multivariate models, including those based on only clinical parameters or bacterial diversity. CONCLUSIONS: In a study of fecal viromes from patients with NAFLD and control individuals, we associated histologic markers of NAFLD severity with significant decreases in viral diversity and proportion of bacteriophages. We developed a model based on fecal viral diversity and clinical data that identifies patients with severe NAFLD and fibrosis more accurately than models based only on clinical or bacterial data.

PubMed ID: 32652145 Exiting the NIEHS site

MeSH Terms: Adult; Aged; Case-Control Studies; Cross-Sectional Studies; Feces/virology; Female; Gastrointestinal Microbiome*; Humans; Intestines/virology*; Liver Cirrhosis/diagnosis; Liver Cirrhosis/virology*; Male; Middle Aged; Non-alcoholic Fatty Liver Disease/diagnosis; Non-alcoholic Fatty Liver Disease/virology*; Prospective Studies; Severity of Illness Index; Virome*; Young Adult

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