Microbiome Influence in Gastric Cancer Progression and Therapeutic Strategies

Jhommara BautistaIvan Maldonado-NoboaDaniela Maldonado-GuerreroLisette Reinoso- QuingaAndrés López-Cortés^*

• Cancer Research Group (CRG), Faculty of Medicine, Universidad de Las Américas, Quito, Ecuador

Gastric cancer (GC) remains a major global health burden, ranking as the fifth most commonly diagnosed malignancy and the fourth leading cause of cancer-related death worldwide. While Helicobacter pylori is established as the primary microbial risk factor, emerging evidence underscores the broader oncogenic potential of gastric microbiome dysbiosis. This review synthesizes recent advances in understanding how microbial communities, both within the stomach and along the gut–stomach axis, contribute to gastric carcinogenesis. We explore how alterations in microbial diversity, virulence, and metabolic output disrupt mucosal homeostasis, drive chronic inflammation, and reshape local immune surveillance. Special attention is given to the molecular mechanisms by which H. pylori virulence factors cytotoxin-associated gene A (CagA) and VacA, vacuolating cytotoxin, induce epithelial transformation, immune evasion, and epigenetic reprogramming. We also highlight the oncogenic roles of non-H. pylori taxa such as Fusobacterium nucleatum, Streptococcus anginosus, and Lactobacillus fermentum, which synergize with host and environmental factors to sustain tumor-promoting microenvironments. Multi-omics studies reveal microbial signatures predictive of disease progression, therapeutic response, and prognosis, laying the foundation for microbiome-informed precision oncology. Furthermore, we examine how microbiota-targeted interventions, probiotics, prebiotics, dietary modulation, and fecal microbiota transplantation, can enhance chemotherapy and immunotherapy efficacy while mitigating treatment-related toxicity. Lastly, we discuss the implications of early H. pylori eradication, the impact of antibiotic resistance, and the need for global surveillance strategies.