The colonic mucosal virome in inflammatory bowel disease reveals Crassvirales depletion and disease-specific virome features.

The mucosal virome is increasingly recognized for its potential role in shaping intestinal health and disease. Building on previous findings, we analyzed the mucosal virome from 51 individuals, including newly diagnosed treatment naïve participants with ulcerative colitis (UC), Crohn's disease (CD), and non-inflammatory bowel disease (non-IBD) controls, incorporating longitudinal sampling for a subset of the participants. Viromes were highly individualized, with no shared or core components across participants. Unlike fecal virome studies, we observed no significant associations between mucosal virome diversity and mucosal inflammation, disease subtype, or sampling site. However, there was positive correlation between virome and bacteriome diversity, particularly in CD, suggesting the presence of dynamic interactions that influence microbial community structure. Crassvirales was abundant in the mucosa layer and, consistent with prior studies, Crassvirales abundance was reduced in IBD, irrespective of inflammation status or IBD subtype. These findings highlight their potential as biomarkers of virome health. Our data also revealed the potential presence of altered bacteriome-virome interactions and longitudinal sampling revealed a persistent subset of viruses, potentially shaping disease progression and remission dynamics. Our study underscores the importance of distinguishing microbial community dynamics across IBD subtypes and highlights Crassvirales as key players in mucosal immunity.