Gut microbiota-derived cholic acid ameliorates lung inflammation in bronchopulmonary dysplasia through modulation of macrophage function.

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