Disrupted Gut Viral-Bacterial Ecology of Patients With Liver Cirrhosis

The gut microbiota contributes to liver cirrhosis (LC), yet the gut virome and its cross-kingdom ecology with bacteria are less well defined.

To characterize LC-associated virome alterations and assess their clinical relevance, we reanalyzed publicly available faecal metagenomes from patients with LC and healthy controls. After quality control and removal of human reads, sequences were mapped to the Chinese Gut Viral Catalogue at 95% nucleotide similarity, viral operational taxonomic units (vOTUs) were annotated using the latest ICTV framework, and viral functions were inferred by KEGG annotation. Differential vOTUs and bacterial species, virus-bacteria networks and random forest classifiers were constructed with internal and external validation.

LC showed reduced viral richness and Shannon diversity, and a distinct Bray-Curtis separation from controls. Ten viral families and 473 vOTUs differed between groups (59 LC-enriched). KEGG-based profiling highlighted functional shifts in LC-enriched viruses, including increased K01185 (lysozyme) and K02172 (blaR1). Virus-bacteria networks were markedly sparser in LC than in controls (130 vs. 509 significant correlations). A virome-based random forest model distinguished patients from controls with high accuracy in internal (optimal AUC = 0.911) and external (optimal AUC = 0.773) validation cohorts, and the model combining viral and bacterial features achieved similarly robust performance.

LC is associated with disrupted gut viral-bacterial ecology, and virome features show promise as non-invasive biomarkers, warranting longitudinal and mechanistic follow-up.