Abstract
The coordinated post-natal development of the gut microbiome and metabolome is essential for preterm infant health, yet its disruption is increasingly linked to adverse outcomes such as bronchopulmonary dysplasia (BPD). In this study, we performed an integrated multiomics analysis of fecal samples collected from preterm infants to characterize temporal changes in gut microbial and metabolic profiles and explore their potential associations with BPD development. This study observed a distinct trajectory of the phylum Bacteroidota as a hallmark of normal gut maturation, with its abundance progressively declining across non-BPD infants. In contrast, infants who later developed BPD exhibited early depletion followed by irregular enrichment of Bacteroidota. Correlation analysis revealed that Streptococcus abundance was positively associated with elevated cysteic acid, a metabolite linked to oxidative stress. Together, these findings suggest that altered Bacteroidota succession and Streptococcus-associated oxidative imbalance may reflect early microbial-metabolic perturbations in infants at risk of BPD. This work provides preliminary, hypothesis-generating insights into gut-associated signatures potentially relevant to BPD pathogenesis. IMPORTANCE: Bronchopulmonary dysplasia (BPD) remains a leading cause of morbidity in preterm infants, yet early biomarkers and targeted preventive strategies are limited. By integrating microbiome and metabolome data from a pilot cohort, this study identified patterns of disrupted Bacteroidota succession and Streptococcus-associated oxidative stress that are associated with BPD risk. These findings highlight the gut as a potential extrapulmonary contributor to disease susceptibility and support early risk assessment and guide future microbiome-targeted interventions in preterm infants.