Lactiplantibacillus plantarum HCS03-001 and Lacticaseibacillus paracasei HCS17-040 Synergize to Combat Helicobacter pylori Colonization and Gastric Inflammation

Abstract Helicobacter pylori infection, affecting over 4.4 billion individuals globally, is a leading cause of chronic gastritis, peptic ulcers and gastric cancer. At present, the standard therapeutic approach for H. pylori infection continues to rely on high-dose antibiotic regimens, despite growing concerns about antibiotic resistance and treatment-associated dysbiosis. Probiotics, particularly Lactobacillus species, have emerged as promising adjuncts due to their multifaceted anti- H. pylori mechanisms. However, only a limited number of existing strains have demonstrated efficacy in treating H. pylori infections. This study investigated the effects of Lactiplantibacillus plantarum HCS03-001 (LP-HCS03) and Lacticaseibacillus paracasei HCS17-040 (LPC-HCS17) against H. pylori using a mouse model. In infected mice, administration of the combined probiotics with 1 × 10 9 CFU each significantly decreased mRNA expression levels of ureA/ureB ( P < 0.001), increased the level of IL-10, and decreased the levels of IL-17 and TNF-α ( P < 0.001), which indicates that the intervention reduced gastric colonization, alleviated inflammation and promoted the restoration of the gastric mucosal barrier. The microbiota in both the stomach and intestines were reconstructed, with particularly pronounced effects observed in the stomach. These findings highlight LP-HCS03 and LPC-HCS17 as promising probiotics to augment H. pylori eradication while preserving microbial homeostasis.