Abstract Background Bronchopulmonary dysplasia (BPD) is a leading cause of chronic lung morbidity in preterm infants, characterized by disrupted alveolar development and persistent inflammation. Although immune and microbial dysregulation contribute to disease pathogenesis, their interaction remains poorly defined. Salivary transcriptomic and microbiome profiling offers a noninvasive approach to elucidate host-microbe dynamics underlying BPD severity and progression. Objective To characterize host inflammatory gene expression and oral microbiome composition in infants with BPD compared with age- and sex-matched healthy controls, and to investigate associations between microbial dysbiosis and inflammatory transcriptomic. Methods We conducted a prospective observational study of 27 infants with established BPD and 15 matched healthy controls. Saliva swabs were collected during clinically stable periods (no acute respiratory infection) for parallel transcriptomic and microbiome profiling. Host gene expression was analyzed using a targeted 590-gene panel focused on inflammation, immune signaling, and airway remodeling pathways (NanoString nCounter). Microbiome composition was characterized via 16S rRNA sequencing. Inflammatory genes with significant overexpression compared with healthy individuals were associated with microbiota. In addition, abundance, alpha/beta diversity, species, and phylum analyses were performed. Correlations between microbial taxa abundance and host transcriptomic signatures (overexpressed) were assessed using multivariate models. Results Infants with BPD exhibited significant upregulation of inflammatory transcripts, including CXCL1 and chemokine signaling genes (p 0.05), compared with healthy controls. Genes involved in neutrophil activation and extracellular matrix remodeling were markedly elevated. Microbiome analysis revealed reduced alpha and beta diversity and a distinct community structure, with increased Neisseria, Prevotella, Fusobacterium, Veillonella, and Streptococcus species and decreased Staphylococcus and commensal Veillonella. Integrated analyses demonstrated correlations between pathogenic taxa and heightened inflammatory gene expression. Compared with BPD Grade 0-1, BPD Grade 2 samples showed enrichment of Toll-like receptor and NF-κB signaling (IRAK1, TRAF6), type II cytokine and Th2 pathways (STAT6), Notch-mediated epithelial remodeling (NOTCH2), and autophagy and interferon-related responses (ATG5, PML, TAP2), indicating persistent innate immune activation, antigen processing, and impaired epithelial repair in more severe disease. Conclusions Integrated host-microbiome analyses reveal distinct proinflammatory transcriptomic signatures and marked oral microbial dysbiosis in infants with BPD. The enrichment of TLR-NF-κB, Th2, autophagy, and interferon-related pathways in BPD Grade 2 compared with Grade 0-1 reflects persistent innate immune activation and impaired epithelial repair as key drivers of disease progression. These findings position salivary multi-omic profiling as a promising noninvasive tool for disease surveillance, early risk stratification, and potential therapeutic targeting in infants at risk for severe BPD. This abstract is funded by: None
Ceballos et al. (2026) studied this question.