A novel exopolysaccharide from Lactobacillus gasseri LGZ1029: Structure elucidation and protective effects against...

Lactic acid bacteria-derived exopolysaccharides (EPS) have shown considerable potential in alleviating intestinal inflammation. However, the therapeutic efficacy of Lactobacillus gasseri EPS against ulcerative colitis (UC) remains largely unexplored. This work identified a novel EPS isolated from L. gasseri LGZ1029, a strain derived from infant feces. Structural analysis revealed that the highly purified fraction LP2^⁎ (53.7 kDa) is a heteropolysaccharide possessing an alternating →6)-α-Glcp-(1 → 2)-α-Manp-(1 → backbone. This structure is substituted at the C2 position of glucopyranosyl residues and mainly comprises mannose, glucose, and galactose in a molar ratio of 74.52:22.46:3.03. In vivo evaluations in a colitis model induced by dextran sulfate sodium (DSS) demonstrated that the partially purified EPS fraction LP2 exerted mucosal protective and anti-inflammatory effects comparable to those of the live probiotic strain. Specifically, LP2 attenuated disease activity index (DAI) scores and body weight loss, alleviated colonic damage, and suppressed inflammation by downregulating MPO, TNF-α, and NF-κB p65, while upregulating IL-10. Furthermore, LP2 modulated gut microbiota composition and restored host metabolic homeostasis, particularly by regulating tryptophan, lipid, sulfate, and organic acid metabolism. These findings provide structural and mechanistic insights into the potential application of L. gasseri EPS as a bioactive dietary ingredient or therapeutic candidate for UC management.