Targeted Next-Generation Sequencing Analysis of BALF Microbiota and Clinical Characteristics in Severe versus Non-Severe Community-Acquired Pneumonia

Background: Severe community-acquired pneumonia (SCAP) is associated with high mortality. However, data on the bronchoalveolar lavage fluid (BALF) microbiota in Chinese SCAP patients remain limited. This study aimed to characterize the clinical features and BALF microbiome composition in patients with SCAP compared to non-severe CAP using targeted next-generation sequencing (tNGS). Methods: We conducted a retrospective study involving 224 CAP and 97 SCAP patients from two hospitals in Shanxi, China (January 2023–January 2025). Clinical characteristics and inflammatory cytokines were compared between groups. BALF samples were analyzed via tNGS to evaluate microbial alpha and beta diversity. Differentially abundant taxa were identified using Linear Discriminant Analysis Effect Size (LEfSe). Results: Compared to the CAP group, SCAP patients were significantly older, had a higher prevalence of comorbidities (hypertension, coronary heart disease, diabetes), and exhibited elevated inflammatory indices (CRP, IL-6, PCT, ESR). SCAP patients also demonstrated a higher likelihood of mixed infections, and the number of detected pathogens showed a positive correlation with the length of hospital stay. tNGS analysis revealed significant differences in alpha diversity and distinct beta diversity clustering between the two groups. LEfSe analysis identified Pseudomonas as a potential biomarker enriched in SCAP, whereas Streptococcus was predominant in CAP. Conclusions: In patients with SCAP, the BALF microbiota showed a significant increase in alpha diversity, which appears to mediate inflammatory cytokine production and is associated with disease worsening. There were pronouned differences between SCAP and CAP in both clinical characteristics and microbiome profiles, highlighting the necessity of integrated diagnostic approaches in pneumonia care. Future research should prioritize delineating the dynamic shifts of microbial communities and their influence on pneumonia severity, with the goal of refining and optimizing treatment strategies.