Metabolic and microbial dysregulation in preterm infants with neonatal respiratory distress syndrome: an early developmental perspective

<bold>Background:</bold> Neonatal respiratory distress syndrome (NRDS) is one of the most severe respiratory disorders in preterm infants (PTIs) due to immature lung development. <bold>Objective:</bold> To delineate the serum metabolic alterations and gut microbiota variations in NRDS and assess their implications on neonatal development. <bold>Methods:</bold> We enrolled 13 NRDS neonates and 12 PTIs, and collected fecal and serum after birth to conduct microbiome and metabolomics, respectively. Longitudinal fecal sampling was executed weekly for a month in NRDS. <bold>Results:</bold> NRDS neonates were characterized by reduced gestational ages and birth weights relative to PTIs. Early postnatal disturbances in tryptophan metabolism were notably in NRDS, concomitant with elevated serum medium- and long-chain fatty acids. Integrative multi-omics analyses revealed an inverse relationship between tryptophan concentrations and Blautia abundance. NRDS neonates manifested cortisol regulation anomalies and augmented hepatic catabolism, correlating with a rise in pro-inflammatory gut taxa. Sequential microbiome profiling reveals delayed evolution of gut probiotics in NRDS. <bold>Conclusions:</bold> The acute perinatal stress leads to mitochondrial compromise, hormonal imbalance, and delayed gut microbiota evolution in NRDS. Despite the short course of NRDS, its impact on neonatal development is significant and requires extended attention.