Polysaccharides from Hippophae rhamnoides L. protected against ethanol-induced gastric ulcer in mice and its impact on metabolites and gut microbiota.

Gastric ulcer (GU) is a common gastrointestinal disorder, and alcohol overdose is one of the main causes of GU. Polysaccharide is considered a promising prebiotic agent to protect against alcohol-induced GU, but its exact mechanisms remain unclear. In this study, Hippophae rhamnoides L. polysaccharides (SP) was exacted and characterized for its structural properties. The gastroprotective effects of SP against ethanol-induced GU were evaluated in a mouse model by administering 200 mg/kg/day SP orally for 14 days. Histological analysis showed that SP significantly decreased gastric lesion areas and ameliorated mucosal injury in mice. These protective effects were mediated by SP-induced inhibition of oxidative stress via the activation of the Nrf2/HO-1 pathway and attenuation of inflammatory responses via the suppression of the TLR4/MyD88/NF-κB pathway. In vitro studies showed that SP mitigated ethanol-induced ROS accumulation and apoptosis in gastric epithelial cells, implying a direct role in protecting against GU. Notably, SP modulated the gut microbiota community and increased probiotic bacterial populations, e.g. Lachnospiraceae and Ruminococcus. These alterations elevated the production of short-chain fatty acids in intestinal tract, particularly acetate and butyrate. Targeted metabolomics showed that SP improved ethanol-induced disturbance of serum metabolites, particularly amino acid metabolism and biosynthesis such as tryptophan, tyrosine, and phenylalanine. Based on the interactions of metabolites within the body, it is speculated that SP protects the integrity of gastric mucosa and tight junctions by modulating microbiota-derived metabolites. This study implies that SP protects against GU via direct effect on the gastric mucosa and modulating the gut-stomach axis.