The Oral-Gastric Microbial Axis in Gastric Cancer: Mechanisms Underlying Development and Progression

The etiology of gastric cancer (GC) is increasingly defined by the complex interplay within the oral-gastric microbial axis. This conceptual shift extends beyond the classical Helicobacter pylori (H. pylori) model. Instead, it encompasses a broader polymicrobial network. Mechanisms underlying ectopic colonization of oral pathobionts are examined alongside their synergistic contributions to mucosal dysbiosis. Remodeling of the tumor microenvironment is discussed through the analysis of critical functional modules, including biofilm formation, metabolic reprogramming, and immune dysregulation. Carcinogenesis is reportedly promoted by specific genotoxic metabolites and perpetuation of chronic inflammation. Diagnostic capabilities are evaluated with a focus on noninvasive biomarkers, where integration of artificial intelligence for risk stratification is identified as a transformative tool for early detection. Furthermore, therapeutic perspectives are expanded by evidence linking microbial composition to the efficacy of immune checkpoint inhibitors and chemotherapy. Strategies for prevention and treatment are proposed based on restoration of microbial homeostasis. Collectively, a roadmap for translating microbiome research into personalized clinical practice for gastrointestinal malignancies is provided by this review.