Lactiplantibacillus plantarum DS1073 protects the gastric mucosa under infection and alcohol stress

Helicobacter pylori (H. pylori) infection and alcohol consumption are major drivers of gastric injury, highlighting the need for non-antibiotic strategies that prevent colonization and preserve mucosal integrity. We screened 340 probiotic-derived cell-free supernatants (CFSs) under microaerophilic conditions, assessed anti-adhesion activity using human antral gastric organoids and organoid-derived epithelial monolayers, and evaluated efficacy in mouse models of acute gastric injury induced by ethanol and hydrochloric acid. Lactiplantibacillus plantarum DS1073 reduced H. pylori viability, inhibited epithelial adhesion, and downregulated key virulence and adhesion genes, including cagA, vacA, ureA, amiE, dupA, hpaA, babA, and ureB. In vivo, both DS1073 CFS and live bacteria decreased gastric colonization and inflammation, improved macroscopic lesion scores, preserved epithelial architecture, restored mucus production, and suppressed expression of acid secretion genes in a mouse model of acute gastric injury. Transcriptome profiling of ethanol-injured human gastric epithelial cells revealed attenuation of cytokine–cytokine receptor interactions, reduced mitogen-activated protein kinase signaling, and normalization of calcium signaling pathways. These findings support DS1073 as a promising non-antibiotic strategy to promote and maintain gastric health, particularly by preventing mucosal damage from chronic infection and acute chemical injury. Clinical evaluation is warranted to assess its preventive and adjunctive potential.