Alterations in the fecal virome and bacteriome-virome interplay in IPAH

Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening cardiovascular disorder characterized by complex multisystem disturbances. Although alterations in the gut microbiota have been reported in IPAH, how the gut virome interacts with bacterial communities and host metabolism remains unclear.

We enrolled 28 patients with IPAH and 30 age-matched healthy controls (HCs). Fecal viromes and bacteriomes were profiled by metagenomic sequencing, and serum metabolomic data were integrated to construct virus-bacterium-metabolite interaction networks. Random forest models were used to evaluate the diagnostic potential of virome features.

IPAH patients exhibited markedly reduced gut virome diversity (Shannon, Simpson, and Pielou indices, p < 0.05) and distinct community structures from HCs (p < 0.01). A total of 499 differential viral operational taxonomic units (vOTUs) were identified, accompanied by extensive reorganization of interaction networks. At the phylum level, Hofneiviricota was enriched and Phixviricota depleted, both correlating with clinical indicators. Virus-bacterium associations were markedly increased in IPAH (44,894 vs. 17,920, r > 0.5). Notably, vOTU2967, vOTU1924, and vOTU4522 were elevated and inversely related to Bacteroides, whose depletion was associated with increased lactic acid levels. Mediation analysis confirmed significant indirect virus-bacterium-metabolite effects (p < 0.05). Random forest models based on vOTUs or viral families effectively distinguished IPAH patients from controls, highlighting the exploratory potential of gut virome features for mechanistic insights.

IPAH is characterized by reduced virome diversity, altered viral taxa, and reorganized virus-bacterium-metabolite networks. These findings suggest that gut viruses may influence disease progression by modulating bacterial metabolism, providing a potential avenue for biomarker discovery and therapeutic intervention.