Microbiome and cancer: mechanistic insights, diagnostic potential, and therapeutic strategies

The human microbiome is now recognized as an active and dynamic participant in cancer biology rather than a passive bystander. Increasing evidence demonstrates that microbial dysbiosis contributes to tumor initiation and progression through chronic inflammation, genotoxic toxin production, metabolic reprogramming, immune modulation, and direct reshaping of the tumor microenvironment. Specific microbial factors including colibactin, Bacteroides fragilis toxin, CagA, and Fusobacterium adhesins intersect with canonical oncogenic pathways. Linking microbial activity to genomic instability and immune evasion. Microbial metabolites such as secondary bile acids, lipopolysaccharide, hydrogen sulfide, and short-chain fatty acids further regulate epithelial integrity, epigenetic remodeling, and immune cell dynamics in a context-dependent manner. Beyond tumorigenesis, the microbiome critically determines therapeutic response. Microbial communities influence chemotherapy and radiotherapy outcomes and shape immune checkpoint blockade efficacy through immune priming, antigen mimicry, and microbiome-metabolite-immune interactions that govern treatment responsiveness. Emerging preclinical studies and early clinical investigations suggest that microbiome modulation, including fecal microbiota transplantation (FMT), may help restore immunotherapy sensitivity in selected patients; however, larger controlled trials are required to establish efficacy, safety, and long-term clinical benefits. This review integrates mechanistic, preclinical, and clinical evidence across microbiome-driven carcinogenesis, tumor microenvironment remodeling, drug metabolism, and biomarker development. Advances in circulating microbial DNA profiling and machine learning-based diagnostics further position the microbiome as both a mechanistic driver and a translational target in precision oncology. We also discuss key challenges, including interindividual variability, standardization of methodologies, and the need for personalized therapeutic strategies. Collectively, understanding and harnessing microbiome-cancer interactions hold significant promise for improving cancer diagnosis, treatment, and patient outcomes.