Preventive and therapeutic effects of an exopolysaccharide produced by Lacticaseibacillus rhamnosus on alcoholic gastric ulcers

Crude exopolysaccharides produced by Lacticaseibacillus rhamnosus SHA113 were previously found to exhibit anti-alcoholic gastric ulcer activity in mice, but their major active fraction, structural characteristics, and underlying mechanisms remain unknown. Here, LRSE1 was identified as the active exopolysaccharide fraction produced by L. rhamnosus SHA113 responsible for the above effects. Purified LRSE1 had a molecular weight of 4.9 × 10⁴ Da and was comprised of L-fucose, D-mannose, D-glucuronic acid, D-glucose, D-galactose, and L-arabinose in the molar ratio of 2.4:6.5:1.2:1.00:0.3:0.6, respectively. The oral administration of LRSE1 resulted in a significant protective and therapeutic effect on alcoholic gastric ulcers in mice. These effects were identified to involve a reduction in reactive oxygen species, apoptosis, and the inflammatory response, increases in antioxidant enzyme activities, and increases in the phylum Firmicutes and decreases in the genera Enterococcus, Enterobacter, and Bacteroides in the gastric mucosa of mice. In vitro experiments showed that the administration of LRSE1 both inhibited apoptosis in GEC-1 cells via the TRPV1-P65-Bcl-2 pathway and inhibited the inflammatory response in RAW264.7 cells via the TRPV1-PI3K pathway. For the first time, we have identified the active exopolysaccharide fraction produced by Lacticaseibacillus that protects against alcoholic gastric ulcers and determined that its effect involves TRPV1-mediated pathways.