Airway microbial dysbiosis and oxidative mitochondrial DNA damage in the development of bronchopulmonary dysplasia

Background This study investigated the association between airway microbiome composition, oxidative mitochondrial DNA (mtDNA) damage, and the development of bronchopulmonary dysplasia (BPD) in preterm infants. Methods A prospective cohort study enrolled 82 VLBW preterm infants (< 32 weeks gestation). Tracheal aspirates (TA) were collected at birth and on postnatal day 28. Airway microbial diversity and composition were assessed using 16S rRNA sequencing. Oxidative mtDNA damage was measured using 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in TA samples. We used PICRUSt2-based metagenome predictions from 16S rRNAgene sequencing of TA samples, with functional pathway annotations based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results Infants who developed BPD (n=25) had lower gestational age, birth weight, and prolonged ventilatory support (p<0.05). Oxidative mtDNA damage was significantly high in infants with BPD, particularly in moderate-to-severe cases (p<0.05). BPD was associated with reduced microbial alpha diversity and distinct beta diversity clustering. Infants with BPD exhibited higher relative abundance of Proteobacteria and lower relative abundance of Firmicutes , with enrichment of Stenotrophomonas, Acinetobacter, and Serratia (p<0.05). By day 28, KEGG-based functional predictions revealed enrichment in microbial pathways related to bacterial motility proteins, circadian rhythm signaling pathway, MAPK signaling pathway, and alpha-linolenic acid metabolism. Proteobacteria abundance correlated positively with oxidative mtDNA damage (r=0.49, p<0.01). Conclusions Airway microbial dysbiosis and oxidative mtDNA damage are strongly associated with BPD severity. Targeting oxidative stress and microbiome modulation may offer potential strategies for BPD prevention and management.