Introduction: Introduction: Necrotizing enterocolitis (NEC) is a severe gastrointestinal disorder primarily affecting preterm neonates, characterized by intestinal inflammation and necrosis. Despite advances in neonatal care, it remains a significant contributor to morbidity, mortality, and long-term complications. Microbial dysbiosis and clinical factors are pivotal in NEC pathogenesis, yet their interactions are not fully understood.

Methodology: A prospective, multicenter cohort study was conducted across four NICUs, enrolling 450 preterm infants (≤32 weeks gestational age). Clinical data were collected on antenatal and postnatal risk factors, feeding practices, and outcomes. Stool samples were analyzed using 16S rRNA sequencing to assess microbial diversity and composition. Multivariate logistic regression was performed to identify risk factors associated with NEC.

Results: Fifty infants (11.1%) developed NEC. Infants with NEC showed significantly reduced microbial diversity, dominated by pathogenic taxa such as Enterobacteriaceae and Clostridia, with decreased beneficial genera like Bifidobacterium and Lactobacillus. Key risk factors included low birth weight, chorioamnionitis, prolonged mechanical ventilation, and formula feeding. Reduced microbial diversity at admission was independently associated with NEC (OR 3.5, p<0.001).

Conclusion: This study underscores the interplay between microbial dysbiosis and clinical risk factors in NEC development. Findings suggest the potential for microbiome-targeted interventions and emphasize the importance of breastfeeding and judicious antibiotic use in reducing NEC incidence.