Abstract
Necrotizing enterocolitis (NEC) is a life-threatening disease in premature infants, characterized by high mortality. Recent studies increasingly highlight the role of gut dysbiosis in NEC pathogenesis. Although probiotics have shown some efficacy in preventing NEC, further research is needed to determine potential strains and approaches. In this study, we demonstrated that the novel probiotic strain Lactobacillus gasseri (L. gasseri) FWJL-4, isolated from the feces of healthy infants, significantly enhanced intestinal barrier function, providing substantial protection against NEC. This protective effect was attributed to elevated intestinal acetate levels. Notably, acetate supplementation alone was sufficient to mitigate NEC, mimicking the protective effects of L. gasseri FWJL-4. Mechanistically, we revealed that L. gasseri FWJL-4 inhibited necroptosis and preserved the number of the goblet cells and enterocytes through the production of the short-chain fatty acid acetate, via activation of the acetate receptors G protein-coupled receptor (GPR) 41 and GPR43. Our findings suggest that L. gasseri FWJL-4 enhances intestinal barrier function to protect against NEC, underscoring the potential of probiotic manipulation as a promising strategy for NEC prevention.