Gut microbiome-enteric virus interactions: mechanisms, clinical implications, and translational directions.

The gut microbiome influences epithelial barrier integrity, metabolite availability, mucosal immune tone, and vaccine responsiveness, all of which are relevant to enterically transmitted viral infection. Norovirus and rotavirus primarily replicate in the intestinal mucosa and cause acute gastroenteritis, whereas poliovirus replicates in the gut and may disseminate systemically. Hepatitis A virus and hepatitis E virus are acquired through the intestine and shed fecally, but their dominant clinical manifestation is hepatitis. This review synthesizes evidence linking the bacteriome, phageome/virome, and mycobiome with these viruses, while explicitly distinguishing direct enteric virus mechanisms from broader microbiome-immune or metabolite pathways and from cross-kingdom evidence extrapolated from intestinal inflammation or pathobiont studies. The strongest evidence supports selected virus-bacterium and virus-metabolite mechanisms, including bacterial glycan interactions in norovirus, bacterial LPS-mediated poliovirus stabilization, bile acid-dependent human norovirus replication in enteroids, and rotavirus-associated barrier disruption. Human studies remain dominated by stool-based associations that are difficult to separate from inflammation, diet, antibiotic exposure, diarrhea, and sampling time. We therefore rank evidence across experimental, organoid, animal, human observational, and clinical-translational levels, and highlight concrete applications for severe gastroenteritis risk prediction, prolonged shedding, impaired barrier recovery, and oral vaccine nonresponse. Future progress will require longitudinal, spatially resolved, multi-kingdom, and multi-omics studies linked to human-relevant experimental systems.