Lower respiratory microbiome and metabolome alterations in pediatric ARDS secondary to community-acquired pneumonia

Abstract

Abstract Background Pediatric acute respiratory distress syndrome (ARDS) is a severe complication of community-acquired pneumonia (CAP) with high mortality, but the microbial and metabolic mechanisms driving its onset remain unclear. This study aimed to characterize these disturbances and identify potential biomarkers of progression using an integrated multi-omics approach. Methods We conducted a multi-omics analysis of bronchoalveolar lavage fluid from 81 children with CAP, including those who progressed to ARDS, using 16 S rRNA gene sequencing and untargeted LC-MS/MS metabolomics. Microbial diversity, community composition, metabolic profiles, and functional predictions were compared between groups, and machine learning was applied to identify predictive metabolic signatures. Paired fecal multi-omics data from a subset of patients were analyzed to explore potential gut–lung interactions. Results The CAP-ARDS group exhibited significantly reduced microbial α-diversity, as indicated by lower Shannon ( p = 0.012), Simpson ( p = 0.015), and Sobs ( p = 0.046) indices, alongside distinct compositional shifts characterized by Pseudomonas enrichment and Streptococcus depletion. Metabolomic profiling identified 83 differential metabolites, with pathway topology analysis highlighting perturbations in pantothenate and CoA biosynthesis, indole alkaloid biosynthesis, and steroid degradation. Terpenoid metabolism emerged as a convergent signal across omics layers: PICRUSt2-based prediction revealed increased terpenoid and polyketide metabolism (adj. p = 0.0642), and 7 terpenoid compounds were among the differential metabolites. Machine learning–selected metabolites demonstrated predictive potential for CAP progression in receiver operating characteristic (ROC) analysis. Correlation analyses based on paired fecal datasets tentatively imply that ectopic gut microbiota translocation may constitute a plausible factor linked to disease progression. Conclusions This multi-omics study reveals marked microbial and metabolic alterations in pediatric CAP patients progressing to ARDS, with convergent terpenoid metabolism and possible gut–lung microbial translocation implicated in pathogenesis. Trial registration This study was registered in the Chinese Clinical Trial Registry (ChiCTR) under the registration number ChiCTR2400089037 on 30 August 2024.