Lacticaseibacillus paracasei NCU-21 improves ethanol-induced gastric mucosal injury by regulating the Nrf2/HO-1 signalling pathway and gastrointestinal microbiota in mice.

Alcohol-induced gastric ulcer (GU) is a gastrointestinal disorder resulting from excessive alcohol consumption. The precise therapeutic effects and underlying mechanisms of Lacticaseibacillus paracasei NCU-21 in ameliorating alcohol-induced GUs remain ambiguous. In this study, we identified and isolated a strain of L.paracasei NCU-21 from the faecal samples of individuals recovering from GU, and evaluated its preventive potential in a murine model of ethanol-induced gastric injury. Supplementation with L.paracasei NCU-21 significantly reduced the ulcer area (p < 0.05) and alleviated gastric mucosal damage. Mechanistically, L. paracasei NCU-21 activated the Nrf2/HO-1 signalling pathway (p < 0.01) and modulated oxidative stress markers, significantly increasing superoxide dismutase (model group vs. high-dose group = 58.76 vs. 162.8, p < 0.001) while reducing the levels of malondialdehyde (model group vs. high-dose group = 2.613 vs. 1.063, p < 0.001) and myeloperoxidase (model group vs. high-dose group = 3.011 vs. 1.708, p < 0.05), thereby mitigating oxidative stress in gastric tissue. Additionally, L. paracasei NCU-21 suppressed gastric inflammation by downregulating the NF-κB signalling pathway (p < 0.05). Furthermore, 16S rRNA sequencing revealed that L.paracasei NCU-21 treatment effectively prevented the dysbiosis of gastrointestinal microbiota associated with alcohol-induced GU. In conclusion, this study innovatively evaluates the effects of L.paracasei NCU-21 in preventing alcohol-induced GU and elucidates its underlying mechanisms, offering theoretical and data support for its clinical application.