Viral-Gut Microbiota Interactions: Implications for the Gut Mucosa in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), arises from complex interactions among genetic susceptibility, immune dysregulation, environmental factors, and the gut microbiome. Bacterial dysbiosis has been extensively studied, whereas the gut virome-comprising eukaryotic viruses and bacteriophages-remains less understood. Viruses can affect the intestinal barrier directly by infecting epithelial and immune cells, or indirectly by reshaping bacterial communities and host immunity. However, current evidence is dominated by cross-sectional associations and animal models, and whether virome alterations drive or result from intestinal inflammation remains unresolved. In this review, we provide a focused overview of intestinal barrier components relevant to IBD, synthesize human and animal evidence on IBD-associated viruses, and distinguish direct viral effects, microbiota-mediated effects, and bidirectional virus-microbiota interactions. We highlight bacteriophage-bacteria interactions as a central and potentially causal axis, discuss UC- and CD-specific differences, and outline causality gaps, search methodology, and emerging therapeutic strategies. Finally, we propose key unresolved questions and future research directions.