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