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

TL;DR

This paper explores how imbalances in the oral-gastric microbial axis contribute to gastric cancer and highlights potential new diagnostic and treatment strategies.

Contribution

The paper introduces the concept of the oral-gastric-gut microbial axis as a broader framework for understanding gastric cancer beyond Helicobacter pylori.

Findings

Declining microbial diversity and harmful microbes contribute to inflammation and cancer development.

Specific microbial patterns could serve as noninvasive tools for early gastric cancer diagnosis.

Microbial composition influences the effectiveness of cancer therapies like immune checkpoint inhibitors.

Abstract

Gastric cancer remains a leading cause of cancer-related death worldwide. While Helicobacter pylori is a well-known risk factor, emerging evidence suggests that broader imbalances in the microbial communities of the mouth, stomach, and gut are significantly associated with disease progression. This article explores the ‘oral-gastric-gut axis’, explaining how specific bacteria and the substances they produce are linked to the disruption of the body’s immune system and metabolism, potentially facilitating tumor growth. We aim to clarify how declining bacterial diversity and expansion of harmful microbes contribute to inflammation and cancer development. These findings are significant, as they identify consistent microbial patterns that could serve as new, noninvasive tools for early diagnosis. Ultimately, understanding these complex interactions provides a foundation for developing novel therapies that target the microbiome to prevent or treat gastric cancer more effectively.

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.

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