Gastric bacterial microbiota and gastric carcinogenesis: from dysbiosis to immune remodeling and therapeutic opportunities

Gastric cancer remains a leading cause of cancer-related mortality worldwide. The classical Helicobacter pylori -centric paradigm of gastric carcinogenesis is being progressively expanded, as it is now recognized that the stomach harbors a complex and metabolically active microbial ecosystem whose compositional shifts fundamentally influence oncogenic progression. This review proposes a unifying dysbiosis-carcinogenesis-immune remodeling-therapeutic intervention (DCIT) framework to integrate the rapidly growing body of evidence linking gastric microbiota dysbiosis to malignancy. We survey the compositional landscape of the gastric microbiota across the Correa cascade, from healthy homeostasis through atrophic gastritis, intestinal metaplasia, and adenocarcinoma, and examine the ecological succession that releases niche constraints for oral commensals and nitrate-reducing taxa in advanced disease stages. We systematically evaluate four complementary mechanistic axes of microbial carcinogenesis: genotoxicity driven by bacterial effectors, chronic inflammation sustained by pattern recognition receptor signaling, epithelial barrier disruption facilitating bacterial translocation, and metabolic reprogramming of the gastric niche generating carcinogenic N -nitroso compounds and secondary bile acids. The review further examines how gastric microbiota remodels the tumor immune microenvironment through immune cell reprogramming, metabolite-mediated signaling, and checkpoint modulation, with direct implications for the efficacy of immune checkpoint inhibitor immunotherapy. The translational pipeline is evaluated from established H. pylori eradication regimens through probiotics, phage therapy, and fecal microbiota transplantation to emerging strategies that integrate microbiota modulation with chemotherapy and immunotherapy. Finally, we assess the methodological challenges of low-biomass gastric microbiome research, the integration of multi-omics platforms, and the critical evidence gaps that need to be addressed to realize the clinical potential of microbiota-targeted strategies for gastric cancer prevention and treatment.