Bronchoalveolar Lavage Fluid Microbial and Metabolic Alterations Associated with Acute Respiratory Distress Syndrome in Hospitalized Patients with Community-Acquired Pneumonia.

Purpose: To characterize bronchoalveolar lavage fluid (BALF) microbiome-metabolome alterations associated with acute respiratory distress syndrome (ARDS) in hospitalized patients with community-acquired pneumonia (CAP). Patients and Methods: Hospitalized patients with CAP were prospectively enrolled and stratified according to ARDS development during hospitalization. BALF was analyzed using 16S rRNA gene sequencing and untargeted metabolomics. Microbial diversity, community composition, and co-occurrence networks were evaluated alongside differential and network-based metabolomic analyses. Weighted co-expression network analysis and integrative multi-omics approaches were used to examine associations among microbiota, metabolites, and clinical traits. The cohort was randomly divided into training and internal validation sets at a 7:3 ratio. A LASSO-selected feature panel was used to develop and compare machine-learning models for distinguishing patients with and without ARDS. Results: Patients with ARDS exhibited greater disease severity and worse short-term clinical outcomes. BALF microbiomes demonstrated reduced alpha diversity, altered community structure, and diminished ecological network connectivity. Metabolomic profiling revealed intergroup separation and differential enrichment of amino acid and bile acid pathways. Integrated analyses identified coordinated microbiota-metabolite-clinical associations linked to ARDS status. A 10-feature signature showed promising discriminatory performance in the training and internal validation sets. Conclusion: ARDS in hospitalized patients with CAP was associated with distinct microbial and metabolic alterations in BALF. Integrated BALF multi-omics profiling may help characterize airway-level pulmonary microenvironmental disturbances associated with CAP-related ARDS.