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Metagenomic analysis of intestinal mucosa revealed a specific eukaryotic gut virome signature in early-diagnosed inflammatory bowel disease.

ABSTRACT: Intestinal dysbiosis is one of the causes underlying the pathogenesis of inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD). Besides bacteria, microbiota comprises both prokaryotic and eukaryotic viruses, that together compose the gut virome. Few works have defined the viral composition of stools, while the virome populating intestinal mucosae from early-diagnosed IBD patients has never been studied. Here we show that, by in-depth metagenomic analysis of RNA-Seq data obtained from gut mucosae of young treatment-naïve patients, early-diagnosed for CD and UC, and from healthy subjects (Ctrl), UC patients display significantly higher levels of eukaryotic Hepadnaviridae transcripts by comparison with both Ctrl and CD patients, whereas CD patients show increased abundance of Hepeviridae versus Ctrl. Moreover, we found that UC gut mucosa is characterized by lower levels of Polydnaviridae and Tymoviridae, whereas the mucosa of patients with CD showed a reduced abundance of Virgaviridae. Our findings support the idea that certain eukaryotic viruses might trigger intestinal inflammation and contribute to IBD pathogenesis and pave the way not only for the discovery of novel diagnostic biomarkers but also for the development of anti-viral drugs for the treatment of IBD.

SUBMITTER: Ungaro F

PROVIDER: S-EPMC6546319 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Metagenomic analysis of intestinal mucosa revealed a specific eukaryotic gut virome signature in early-diagnosed inflammatory bowel disease.

Ungaro Federica F Massimino Luca L Furfaro Federica F Rimoldi Valeria V Peyrin-Biroulet Laurent L D'Alessio Silvia S Danese Silvio S

Gut microbes 20180925 2

Intestinal dysbiosis is one of the causes underlying the pathogenesis of inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD). Besides bacteria, microbiota comprises both prokaryotic and eukaryotic viruses, that together compose the gut virome. Few works have defined the viral composition of stools, while the virome populating intestinal mucosae from early-diagnosed IBD patients has never been studied. Here we show that, by in-depth metagenomic analysis ...[more]

PMID: 30252582

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Project description:Background & aimsAlterations 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.MethodsIn 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.ResultsPatients 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.ConclusionsIn 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.

Dataset Information

Metagenomic analysis of intestinal mucosa revealed a specific eukaryotic gut virome signature in early-diagnosed inflammatory bowel disease.

Publications

Metagenomic analysis of intestinal mucosa revealed a specific eukaryotic gut virome signature in early-diagnosed inflammatory bowel disease.

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