Characterizing the gut virome in ulcerative colitis and crohn’s disease: signatures of disease severity

BACKGROUND: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic disorder marked by intestinal inflammation and immune dysregulation. While bacterial dysbiosis has been widely investigated, the gut virome remains less explored. Altered viral communities, particularly bacteriophages, may destabilize microbial balance and amplify host inflammation. METHODS: To characterize virome alterations, we conducted a cross-sectional observational study in Tabriz, Iran, involving fifty participants divided into five groups: mild UC, severe UC, mild CD, severe CD, and healthy controls. Stool samples were processed for viral nucleic acid extraction and analyzed using metagenomic next-generation sequencing. Bioinformatics pipelines included diversity assessment, taxonomic profiling, functional annotation, and discriminant analysis (LEfSe). Predictive modeling was performed with random forest classifiers. RESULTS: Virome richness and diversity were reduced in severe UC and CD compared with controls, whereas mild cases showed values closer to healthy individuals. Taxonomic profiling revealed depletion of crAss-like phages and microviridae in IBD, along with enrichment of Caudovirales families such as siphoviridae and myoviridae. Among eukaryotic viruses, anelloviridae were prominent in severe IBD, and herpesviridae were enriched specifically in severe UC. Functional annotation highlighted enrichment of structural and lytic phage proteins in severe groups, whereas lysogeny-associated domains were more abundant in healthy controls. Random forest models based on viral features achieved appropriate accuracy, with an AUC of 0.89 for distinguishing IBD from controls and 0.83 for classifying mild versus severe disease. CONCLUSION: Thus, IBD is associated with reduced virome diversity, loss of core protective phages, and selective enrichment of bacteriophages and eukaryotic viruses. These findings suggest that virome features may have potential as biomarkers for non-invasive diagnosis and severity stratification in IBD, requiring validation in larger and longitudinal cohorts.