Research advances in gut bacteria dysbiosis and neonatal necrotizing enterocolitis

As a severe gastrointestinal disease with multiple causative factors, necrotizing enterocolitis (NEC) is one of the most common devastating necro-inflammatory intestinal injuries in neonates, particularly among preterm or very-low-birth-weight infants. Prematurity, formula feeding, bacterial colonization and proliferation are the major risk factors. The incidence of NEC is 5-10% among very-low-birth-weight neonates and the mortality 20-30%. Recent studies suggest that NEC results from gut bacteria dysbiosis activating an uncontrolled proinflammatory response. In gut microbiota composition of preterm infants, there are more potential pathogens of Enterobacteriaceae, Staphylococcus, Enterococcus and Clostridium. And there is a paucity of beneficial commensal organisms such as strict anaerobic bacteria (esp. Negativicutes), Bifidobacterium and Propionibacterium. Also the diversity of microbiota declines. To date, there is no consensus on which specific bacterial strains are causally correlated with NEC development. Several prospective studies have shown a marked dysbiosis with phylum Proteobacteria before NEC onset. Lipopolysaccharide (LPS), a product of Gram-negative Proteobacteria, activates TLR4 signaling pathway of mediating an exaggerated inflammatory response. In addition, an interaction between gut bacteria dysbiosis and an immature intestine has also been implicated in the pathogenesis of NEC. Thus some researchers hypothesized that inappropriate colonization of premature intestine may be a major predisposing factor for NEC. The administration of probiotics such as Bifidobacterium and Propionibacterium may mitigate the damage caused by gut bacteria dysbiosis through activating NOD2 signaling pathway or regulating lymphocyte balance. Thus it may help devise a new strategy for early protection of NEC. Key words: Neonate; Necrotizing enterocolitis; Gut bacteria dysbiosis