Unveiling the Gastric Microbiome: Novel Insights into Early Detection and Pathogenesis of Gastric Cancer.

Gastric cancer (GC) remains a major global health burden and is frequently diagnosed at advanced stages owing to the limited sensitivity, invasiveness, and restricted availability of current screening strategies. Increasing evidence indicates that the gastric microbiome including Helicobacter pylori and diverse non-H. pylori bacteria, fungi, and viruses actively contribute to gastric carcinogenesis by modulating mucosal immunity, chronic inflammation, epithelial barrier integrity, and metabolism. High-throughput sequencing has revealed reproducible dysbiosis signatures in GC, characterized by enrichment of taxa such as Lactobacillus, Streptococcus, and Fusobacterium, and depletion of beneficial commensals, including Bifidobacterium and short-chain fatty acid producing anaerobes, some of which show promise as diagnostic or prognostic biomarkers. This review summarizes current knowledge on bacterial, fungal, and viral inhabitants of gastric tumors, highlighting their mechanistic roles in tumor initiation and progression and their potential as microbial indicators of disease. It further evaluates noninvasive and minimally invasive early detection strategies based on fecal and salivary microbiota profiling, urinary extracellular vesicles, and metabolomic fingerprints, alongside multi-omics integration and machine-learning models that combine microbial and host features to improve risk stratification. Finally, the review discusses therapeutic avenues including microbiota modulation, immunotherapy microbiome interactions, and personalized medicine frameworks that incorporate microbial signatures into clinical decision-making, underscoring the need for standardized, multicenter studies to translate gastric microbiome insights into robust tools for early detection and targeted intervention in GC.