Gut microbiota and short-chain fatty acids in the pathogenesis of necrotizing enterocolitis in very preterm infants

The development of a symbiotic gut ecosystem is a crucial step in postnatal adaptation. The gut microbiome of very preterm infants is characterized by an overall instability, reduced microbial diversity, and a predominance of Gram-negative Proteobacteria, all factors associated with an increased risk of necrotizing enterocolitis (NEC). Short-chain fatty acids (SCFAs) are the key bacterial metabolites that are essential for maintaining intestinal homeostasis, supporting immune development, enhancing intestinal barrier integrity, and reducing inflammation. This review examines the role of gut microbiota and SCFAs in neonatal NEC, with a focus on potential diagnostic and therapeutic strategies. Clinical studies have consistently demonstrated a significant decrease in total SCFA levels and individual bacterial metabolites in preterm infants with NEC. This finding has been corroborated by various experimental models. Clarification of the role of SCFAs in NEC pathogenesis, determination of their diagnostic utility, and assessment of the feasibility of developing comprehensive pro- and postbiotic formulations require multi-center, multi-omics investigations that include a large cohort of very preterm infants.