Pneumocystis jirovecii associated with Lung Virome in patients with severe pneumonia

Pneumocystis jirovecii (P. jirovecii) threatens immunocompromised patients, yet its role in the lung microbiome remains unclear. We performed metagenomic sequencing on bronchoalveolar lavage fluid from two retrospective cohorts: a multicenter study of 1,737 patients with pneumonia and a validation cohort of 72 intubated ICU patients. Participants were categorized into P. jirovecii infection, colonization, or negative groups based on qPCR and clinical characteristics. Our analysis revealed minimal bacterial differences but significant viral and fungal variations. Notably, negative patients with P. jirovecii exhibited the lowest viral diversity. Even after adjusting for potential confounders, including immunosuppression and disease severity, P. jirovecii status remained most strongly associated with virome alterations. Furthermore, in cytomegalovirus-positive individuals, P. jirovecii positivity was significantly associated with higher 28-day mortality. These findings suggest that P. jirovecii colonization represents a distinct intermediate state in the lung microbial ecosystem between infection and negative, shedding light on its potential role in pneumonia pathogenesis and outcomes.