Cross-cohort analysis reveals conserved gut virome signatures and phage-encoded auxiliary functions in ulcerative colitis

Abstract While gut bacteriome dysbiosis is a well-established hallmark of ulcerative colitis (UC), the ecological and functional remodeling of the gut virome conserved across diverse populations remains unclear. Here, by constructing a cross-cohort atlas of the UC-associated fecal virome, we show that viral reorganization closely parallels bacterial dysbiosis, with enrichment of phages targeting disease-associated bacterial taxa. We identified a conserved set of UC-associated viral signatures that robustly distinguished UC from healthy controls using machine-learning-based classification across independent cohorts. Functional profiling further revealed that phages enriched in UC carried higher densities of auxiliary metabolic genes (AMGs) related to virulence and antibiotic resistance than phages depleted in UC, with immune evasion and glycopeptide resistance genes particularly overrepresented. Together, our cross-cohort approach highlights the value of the gut virome-based diagnostic framework for UC and suggests that phage-encoded AMGs may contribute to shaping the gut ecosystem under inflammatory conditions.