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• W2794207786 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 (gut virome). Although many works defined the gut virome of stools, the viral community of intestinal mucosae from IBD patients is understudied. We profiled the entire eukaryotic viral populations of gut mucosal samples from early-diagnosed patients with IBD to uncover viral species associated with disease onset. Publicly available RNA-seq data were retrieved from NCBI GEO (GSE57945). FASTQ reads of gut mucosae from young (2–17 years) naïve patients, early-diagnosed for CD (n = 243) and UC (n = 73), and from healthy subjects (n = 43, Ctrl) were adaptor trimmed, quality controlled, and mapped to the hg38 human reference genome with TopHat for splicing specific alignment. Unaligned reads were used for metagenomic analysis. Viral reads were visualised with Integrative Genomics Viewer (IGV; Broad Institute). Functional enrichment for Gene Ontology (GO) biological processes was performed with the Gene Set Enrichment Analysis (GSEA) software. Specific viral transcript abundance was confirmed in a validation cohort of patients by qRT-PCR. Statistical analysis was performed with IBM SPSS and Graph Pad 7-Prism. By GSEA analysis, GO data sets related to virus response were enriched in IBD patients compared with controls. Such enrichment was associated with specific eukaryotic viral infections of mucosal samples. In fact, UC patients displayed higher levels of eukaryotic Hepadnaviridae transcripts by comparison with both Ctrl (p = 0.004) and CD patients (p = 0.0001), indicating this viral family to specifically characterise UC virome in the early stage of the disease. In contrast, CD patients showed higher levels of Hepeviridae by comparison with Ctrl (p = 0.002), suggesting this eukaryotic family as a candidate triggering stimulus in CD patients. Interestingly, Hepadnaviridae in UC negatively correlated with Polyadnaviridae and Tymoviridae (R2 = −0.25, p < 0.00001; R2 = −0.11, p < 0.00001), whereas in CD Hepeviridae negatively correlated with Virgaviridae (R2 = −0.25; p < 0.00001), indicating that, in IBD-specific viromes, some viral entities prevail over others. Finally, these results were validated in a separate cohort of patients. Our results indicated that specific eukaryotic viral infections occurring in both early UC and CD patients may underlie IBD aetiogenesis. Further analysis demonstrating the role of these viruses in triggering intestinal inflammation may open new frontiers in early IBD therapy exploiting specific antiviral drugs to control intestinal inflammation." @default.
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• W2794207786 date "2018-01-16" @default.
• W2794207786 modified "2023-09-25" @default.
• W2794207786 title "DOP016 Metagenomic analysis of intestinal mucosa revealed an IBD-specific shift in the eukaryotic gut virome composition at early stages of gut inflammation" @default.
• W2794207786 doi "https://doi.org/10.1093/ecco-jcc/jjx180.053" @default.
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