Abstract

This study explores the impact of gut microbiota-derived metabolites on bronchopulmonary dysplasia (BPD) pathogenesis, focusing on their roles in macrophage plasticity and inflammation. In a prospective nested case-control cohort of 30 BPD infants and 33 preterm controls, 16S rRNA and mass spectrometry analyses identified seven differential gut bacterial genera, with depleted Streptococcus and enriched Klebsiella in BPD patients, alongside reduced fecal and serum cholic acid. In chorioamnionitis-induced rat BPD models, cholic acid supplementation alleviated lung inflammation by regulating macrophage migration and polarization. RNA-seq and in vitro experiments revealed cholic acid acts via inhibiting HIF-1α expression and transcriptional activity, which was abolished by HIF-1α silencing. These findings connect gut microbiota to BPD, highlighting cholic acid as a key regulator of macrophage function through the HIF-1α pathway to mitigate inflammation, providing new clues for understanding and intervening in BPD.