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

Abstract

Gastric cancer (GC), often diagnosed at advanced or metastatic stages, remains a significant clinical challenge requiring novel biomarkers for early detection, risk stratification, and effective, personalized treatment optimization. Emerging evidence underscores a strong association between gut microbiome dysbiosis and GC initiation, progression, and therapeutic outcomes. This review explores the potential of the advanced/metastatic gastric microbiome as a source of diagnostic and targetable biomarkers and its role in modulating responses to immunotherapy. Although <i>Helicobacter pylori</i> (<i>H. pylori</i>) is the most significant risk factor for GC, several other gastrointestinal taxa&mdash;including <i>Fusobacterium nucleatum</i> (<i>F. nucleatum</i>)&mdash;have been implicated in advanced GC (AGC). At its inception, microbial dysbiosis contributes to chronic inflammation and immune evasion, thereby influencing tumor behavior and treatment efficacy. Integrating microbiome-based biomarkers into risk stratification, GC staging, and targetable treatment frameworks may enhance early detection, inform immunotherapy strategies, and improve patient-specific treatment responses. <i>Bifidobacterium</i> and <i>Lactobacillus rhamnosus GG</i> have the potential to change the immunotherapy framework with their direct influence on dendritic cell (DC) and cytotoxic T cell (CTL) activity. However, clinical translation is impeded by methodological heterogeneity, causality limitations, and a lack of clinical trials. Nonetheless, the integration of microbiome profiling and the development of therapeutic microbiome modulation strategies, such as personalized probiotics regimens and fecal microbiota transplantation, hold substantial potential for improving clinical outcomes and reducing treatment-related toxicity in GC management.