The association between neonatal respiratory distress syndrome and gut microbiota dysbiosis: evidence from metagenomics

Abstract

Objective Neonatal respiratory distress syndrome (NRDS) is a common and life-threatening respiratory disorder that affects newborns, significantly impacting their health and survival rates. In recent years, the potential role of the gut-lung axis in NRDS has garnered increasing attention; however, the specific mechanisms involved remain unclear. This study aimed to investigate the association between NRDS and gut microbial composition and functional profiles using shotgun metagenomic sequencing. Methods This case–control study recruited 25 infants diagnosed with NRDS and 15 healthy newborns, all aged between 2 and 6 days. Fecal samples were collected from all participants for subsequent metagenomic sequencing and bioinformatics analysis. Results There was no significant difference in α-diversity between the NRDS group and the control (CON) group (p = 0.3335). However, β-diversity exhibited a significant difference (p = 0.001). In the NRDS group, the gut microbiota was enriched with Bacillota, Klebsiella, and Enterococcus, while Bifidobacterium and butyrate metabolism-related bacteria (Bacteroides/Butyricicoccus) were significantly reduced (p < 0.05). Functional analysis indicated that Staphylococcus aureus infection and the Phosphotransferase system (PTS) pathway were enriched in the NRDS group, whereas Butanoate metabolism and Glutathione metabolism were significantly enriched in the CON group. A 10-species classifier achieved 96% AUC for NRDS prediction. Conclusion NRDS was associated with differences in gut microbial composition and shotgun-metagenomic functional profiles. These preliminary findings characterize group-level microbial differences but do not establish whether the observed alterations preceded or resulted from NRDS. Longitudinal studies are required to clarify their temporal relationship and clinical relevance.