The cross-talk between the metabolome and microbiome in a double-hit neonatal rat model of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD), a chronic lung disease in preterm infants, is associated with inflammation and high oxygen exposure. However, the effects of antenatal inflammation and postnatal extended hyperoxia on the metabolome and microbiome remain unclear. In this study, pregnant rats received lipopolysaccharide or saline injections on gestational day 20 and were exposed to either 21 % or 80 % oxygen for 4 weeks post-birth. Analysis revealed an increase in Firmicutes, Proteobacteria, and Actinobacteria, with a decrease in Bacteroidetes in BPD rats. Metabolomic analysis identified 78 altered metabolites, primarily lipids, enriched in pathways including arginine biosynthesis, sphingolipid metabolism, and primary bile acid biosynthesis in BPD rats. Integration analysis revealed strong correlations between intestinal microbiota and metabolites in BPD rats. These findings underscored the impact of antenatal inflammation and prolonged postnatal hyperoxia on gut microbiota and serum metabolome, suggesting their role in BPD pathogenesis.