{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:55:05Z","timestamp":1793332505170,"version":"4.5.0"},"reference-count":164,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>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 <jats:italic>Helicobacter pylori<\/jats:italic> 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\u2013stomach 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 <jats:italic>H. pylori<\/jats:italic> 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-<jats:italic>H. pylori<\/jats:italic> taxa such as <jats:italic>Fusobacterium nucleatum<\/jats:italic>, <jats:italic>Streptococcus anginosus<\/jats:italic>, and <jats:italic>Lactobacillus fermentum<\/jats:italic>, 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 <jats:italic>H. pylori<\/jats:italic> eradication, the impact of antibiotic resistance, and the need for global surveillance strategies.<\/jats:p>","DOI":"10.3389\/fmed.2025.1681824","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T05:24:32Z","timestamp":1760937872000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["Microbiome influence in gastric cancer progression and therapeutic strategies"],"prefix":"10.3389","volume":"12","author":[{"given":"Jhommara","family":"Bautista","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Maldonado-Noboa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Maldonado-Guerrero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisette","family":"Reinoso-Quinga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"L\u00f3pez-Cort\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1007\/s12672-025-02802-x","article-title":"Deciphering the dual role of autophagy in gastric cancer and gastroesophageal junction cancer: from tumor suppression to cancer progression","volume":"16","author":"Lei","year":"2025","journal-title":"Discov Oncol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1007\/s10585-021-10144-5","article-title":"Early career leadership Council of the Metastasis Research Society. 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