Metagenomic and transcriptomic analysis of bronchoalveolar lavage fluid from patients with P. Jirovecci infection and those with colonization

Pneumocystis jirovecii pneumonia (PJP) is a severe infection in immunocompromised children. This study explored the interactions between pathogen features of P. jirovecii, the lung microbiota, and immune responses, and their impact on disease severity and outcomes in pediatric patients with PJP. In this observational study, bronchoalveolar lavage fluid (BALF) samples were collected from a cohort of 50 children, including 22 with PJP and 28 with P. jirovecii colonisation (PJC). Microbiome and transcriptomic analyses were performed to assess the relationships between lung pathogens, microbial composition, host immune response, and clinical outcomes. Patients with PJP demonstrated a distinct lung microbiome profile compared with patients with PJC, characterised by an imbalance in microbial composition, particularly with an increased presence of opportunistic bacteria. Host transcriptomic analysis revealed a key role of CD4⁺ lymphocytes and inflammatory pathways, including reduced IL-17 signalling and neutrophil activation, which impaired pathogen clearance. This dysregulated immune response led to sustained hyperinflammation, contributing to more severe PJP cases and higher mortality rates. The study highlights that microbial dysbiosis and immune dysregulation are closely linked to disease severity and outcomes in paediatric patients with PJP and provides characteristics through which we can better distinguish early PJP from PJC.