Gut virome and metabolic associations in patients with acute pancreatitis

Acute pancreatitis (AP) is a frequent inflammatory disorder with outcomes ranging from mild disease to severe forms marked by infection and organ failure. Gut microenvironment disruption and barrier dysfunction are increasingly recognized as key drivers of AP progression, yet most microbiome studies have focused on bacteria. The gut virome modulates bacterial ecology and host immune responses and remains poorly characterized in AP. We aimed to comprehensively profile virome alterations in AP and evaluate their associations with disease severity, etiology, and clinical parameters. Metagenomic sequencing data from AP patients and healthy controls (HCs) were analyzed using the viromic tools. Viral diversity, taxonomy, functional composition, and predicted viral-host linkages were profiled. Microbial-viral-metabolite networks were constructed, and classification performance was evaluated using random forest models. AP viromes exhibited significantly reduced Shannon and Simpson diversity and distinct β-diversity separation from HCs. AP-enriched phages predominantly targeted Parabacteroides, Escherichia, and Bacteroides, while HC-enriched phages were linked to SCFA-producing commensals. Functional analysis revealed enrichment of replication- and lysis-related auxiliary metabolic genes (AMGs) in AP-enriched viral operational taxonomic units (vOTUs), whereas HC-associated vOTUs carried stability-related functions. Severity- and etiology-stratified analyses indicated consistent enrichment of <i>Peduoviridae</i> infecting Enterobacteriaceae and higher prevalence of eukaryotic viruses in advanced stages. Network analyses revealed denser microbial-viral-metabolite interactions in AP, correlated with hepatobiliary and lipid metabolic markers. A minimal seven-virus panel achieved an AUC of 97.5% for AP classification. AP is characterized by profound gut virome remodeling reflecting disease severity and etiology, with diagnostic and mechanistic relevance for future therapeutic strategies.IMPORTANCEThis study highlights the gut virome as a previously underappreciated component of acute pancreatitis (AP)-associated dysbiosis and suggests that viral communities may influence disease severity and metabolic disturbances beyond bacterial effects alone. By demonstrating the diagnostic potential of virome-based signatures, our findings support expanding microbiome research in AP to include viral components, with implications for improved disease stratification and future therapeutic development.