From dysbiosis to precision oncology: translational role of the microbiome in gastrointestinal cancer.

Gastrointestinal (GI) cancers, including colorectal, gastric, pancreatic, hepatocellular, and esophageal malignancies, remain a leading cause of cancer-related mortality worldwide. Emerging evidence identifies the gut microbiome as a critical regulator of GI carcinogenesis, influencing tumor initiation, immune evasion, therapeutic response, and clinical outcomes through inflammation, genotoxicity, metabolic reprogramming, and epithelial barrier disruption. Importantly, biological rationale, clinical evidence, and translational opportunities differ across GI tumor types. Specific taxa, including Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, pks+ Escherichia coli, and Helicobacter pylori, exhibit tumor-specific oncogenic roles with causal evidence ranging from associative to guideline-validated. Microbiome-based biomarkers, including composite multi-taxon models and signatures predictive of immune checkpoint inhibitor response, are evaluated using a four-tier framework (preclinical, associative, near-clinical, and validated). Microbiome-targeted therapies, including probiotics, fecal microbiota transplantation, dietary modulation, and engineered microbial therapeutics, are critically appraised according to clinical evidence and translational readiness. Advances in spatial microbiomics, single-cell analysis, multi-omics, and artificial intelligence may further accelerate microbiome-based precision oncology. This review provides a translationally stratified synthesis of microbiome-GI cancer interactions and their implications for precision oncology.