TY - JOUR
T1 - Intestinal Virome Signature Associated With Severity of Nonalcoholic Fatty Liver Disease
AU - Lang, Sonja
AU - Demir, Münevver
AU - Martin, Anna
AU - Jiang, Lu
AU - Zhang, Xinlian
AU - Duan, Yi
AU - Gao, Bei
AU - Wisplinghoff, Hilmar
AU - Kasper, Philipp
AU - Roderburg, Christoph
AU - Tacke, Frank
AU - Steffen, Hans Michael
AU - Goeser, Tobias
AU - Abraldes, Juan G.
AU - Tu, Xin M.
AU - Loomba, Rohit
AU - Stärkel, Peter
AU - Pride, David
AU - Fouts, Derrick E.
AU - Schnabl, Bernd
N1 - Publisher Copyright:
© 2020
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - Biomarker
KW - Microbiota
KW - Prognostic Factor
KW - Progression
UR - http://www.scopus.com/inward/record.url?scp=85096171868&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2020.07.005
DO - 10.1053/j.gastro.2020.07.005
M3 - Article
C2 - 32652145
AN - SCOPUS:85096171868
SN - 0016-5085
VL - 159
SP - 1839
EP - 1852
JO - Gastroenterology
JF - Gastroenterology
IS - 5
ER -