Gut Microbiome in Neonatal Necrotizing Enterocolitis - A Comprehensive Review of Evidence

Necrotizing enterocolitis (NEC) is one of the most catastrophic gastrointestinal emergency occurring predominantly in preterm neonates. It contributes to substantial neonatal morbidity and mortality. Disturbances in the intestinal microbiome are crucial to disease pathogenesis. In preterm infants, an immature intestinal barrier, dysregulated immune responses, and environmental exposures altogether predispose to alteration in microbial colonization and intestinal inflammation. This review was done to present the current evidence on gut microbiome alterations associated with NEC in preterm infants. A systematic search of the MEDLINE and EMBASE databases was performed using search strategy related to prematurity, intestinal microbiota, and necrotizing enterocolitis. A total of 42 studies assessing microbial composition, microbial progression, or microbial functional patterns in relation to NEC were included. Across the included studies, NEC was commonly preceded by reduced microbial diversity, delayed maturation of anerobic communities, and expansion of Proteobacteria, particularly Enterobacteriaceae family such as Klebsiella and Escherichia. Longitudinal studies further showed that these microbial changes may become evident days to weeks before clinical disease, suggesting a potential window for early risk identification. Functional analyses also showed alterations in microbial metabolic pathways, including short-chain fatty acids, tricarboxylic acid intermediates, volatile compounds, and viral signatures that may lead to epithelial injury and inflammatory signaling. Clinical and environmental factors including antibiotic exposure, mode of delivery, feeding practices, and NICU microbial ecosystem are important determinants of neonatal gut microbiome development. Thus, the current evidence supports a reproducible pattern of intestinal dysbiosis preceding NEC. Better understanding of microbiome dynamics may aid early risk stratification and support microbiome-targeted preventive strategies in vulnerable preterm populations.