Microbiome Signatures in Gastric Cancer: Emerging Biomarkers for Risk Stratification, Therapy Guidance, and Prognostic Insight

Gastric cancer (GC), frequently diagnosed at advanced/metastatic stages, necessitates the identification of novel biomarkers for early detection and optimized treatment strategies. Emerging research suggests a strong association between gut microbiome alterations and GC development, progression, and therapeutic response. This study explores the potential of the gastric microbiome as a source of biomarkers to predict GC prognosis and progression, while also assessing its modulatory influence on first-line treatments for metastatic disease. Beyond Helicobacter pylori, other bacterial taxa such as Fusobacterium, Lactobacillus, and Peptostreptococcus have been implicated in carcinogenesis and immune modulation. Microbial dysbiosis is increasingly linked to chronic inflammation, immune evasion, and altered drug metabolism, which may influence tumor dynamics and therapeutic outcomes. Microbiome-based biomarkers offer promising avenues for early GC detection, particularly in H. pylori-negative cases, and may enhance response prediction to immunotherapies, including PD-1/PD-L1 inhibitors. However, critical challenges remain, including a lack of methodological standardization, confounding variables like diet and antibiotic use, and unresolved issues around causation versus correlation. Despite these hurdles, the integration of microbiome data with other omics platforms (e.g., transcriptomics, metabolomics, ctDNA) holds significant promise for refining predictive models. Furthermore, therapeutic modulation of the microbiome, via probiotics, fecal microbiota transplantation, or diet may offer novel strategies to enhance treatment efficacy and reduce toxicity in GC management.