AP is characterized by profound gut virome remodeling reflecting disease severity and etiology, with diagnostic and mechanistic relevance, and a minimal seven-virus panel achieved an AUC of 97.5% for AP classification.
Key Findings
Results
AP patients exhibited significantly reduced gut virome alpha diversity compared to healthy controls.
Shannon and Simpson diversity indices were both significantly reduced in AP patients relative to healthy controls (HCs).
Beta-diversity analysis showed distinct separation between AP and HC viromes.
Metagenomic sequencing data were analyzed using viromic tools to profile viral diversity, taxonomy, functional composition, and predicted viral-host linkages.
Results
AP-enriched phages predominantly targeted pathogenic or opportunistic bacterial genera, while HC-enriched phages were linked to SCFA-producing commensals.
AP-enriched phages predominantly targeted Parabacteroides, Escherichia, and Bacteroides.
HC-enriched phages were linked to short-chain fatty acid (SCFA)-producing commensal bacteria.
Predicted viral-host linkages were profiled as part of the metagenomic analysis pipeline.
Results
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.
AP-enriched vOTUs were enriched in replication- and lysis-related AMGs.
AMG functional composition was assessed as part of the virome functional profiling.
Results
Severity- and etiology-stratified analyses indicated consistent enrichment of Peduoviridae infecting Enterobacteriaceae and higher prevalence of eukaryotic viruses in advanced AP stages.
Peduoviridae infecting Enterobacteriaceae were consistently enriched across severity and etiology subgroups.
Eukaryotic viruses showed higher prevalence in more advanced stages of AP.
Both disease severity and etiology were used as stratification variables in subgroup analyses.
Results
Network analyses revealed denser microbial-viral-metabolite interactions in AP patients, correlated with hepatobiliary and lipid metabolic markers.
Microbial-viral-metabolite networks were constructed and showed denser interactions in AP compared to HCs.
These interactions were correlated with hepatobiliary and lipid metabolic markers.
Network construction integrated microbiome, virome, and metabolite data.
Results
A minimal seven-virus panel achieved an AUC of 97.5% for classifying AP patients from healthy controls.
The seven-virus diagnostic panel achieved an area under the receiver operating characteristic curve (AUC) of 97.5%.
Classification performance was evaluated using random forest models.
This minimal viral signature was derived from the broader virome profiling dataset.
Discussion
The gut virome is a previously underappreciated component of AP-associated dysbiosis with potential influence on disease severity and metabolic disturbances beyond bacterial effects alone.
Most prior microbiome studies in AP have focused on bacteria, leaving the virome poorly characterized.
The study suggests viral communities may influence disease severity and metabolic disturbances independently of bacterial effects.
Findings support expanding microbiome research in AP to include viral components for improved disease stratification and therapeutic development.
Liu M, Wang L, Liu J, Yuan Q, Zhang Y, Wu S, et al.. (2026). Gut virome and metabolic associations in patients with acute pancreatitis.. mSystems. https://doi.org/10.1128/msystems.01400-25