Lang, Sonja, Demir, Muenevver, 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, Starkel, Peter, Pride, David, Fouts, Derrick E. and Schnabl, Bernd (2020). Intestinal Virome Signature Associated With Severity of Nonalcoholic Fatty Liver Disease. Gastroenterology, 159 (5). S. 1839 - 1853. PHILADELPHIA: W B SAUNDERS CO-ELSEVIER INC. ISSN 1528-0012

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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 chol-angitis 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Lang, SonjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Demir, MuenevverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martin, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jiang, LuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, XinlianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Duan, YiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gao, BeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wisplinghoff, HilmarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kasper, PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roderburg, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tacke, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steffen, Hans-MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goeser, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abraldes, Juan G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tu, Xin M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loomba, RohitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Starkel, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pride, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fouts, Derrick E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schnabl, BerndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-312694
DOI: 10.1053/j.gastro.2020.07.005
Journal or Publication Title: Gastroenterology
Volume: 159
Number: 5
Page Range: S. 1839 - 1853
Date: 2020
Publisher: W B SAUNDERS CO-ELSEVIER INC
Place of Publication: PHILADELPHIA
ISSN: 1528-0012
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HUMAN GUT; MICROBIOTA; FIBROSIS; PREDICTION; MORTALITY; BACTERIA; NAFLDMultiple languages
Gastroenterology & HepatologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/31269

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