From Dysbiosis to Symbiosis: Using the Gut Microbiome to Improve Cancer Outcomes

The gut microbiome has emerged as an important regulator of cancer biology, influencing carcinogenesis, treatment response, and therapy-related toxicity. This narrative review synthesizes current evidence on the mechanistic roles of the gut microbiota in gastrointestinal (GI) cancers and evaluates emerging microbiome-based strategies for improving cancer outcomes. Dysbiosis—characterized by altered microbial diversity, depletion of beneficial functions, and enrichment of disease-associated taxa—may contribute to tumorigenesis through interconnected mechanisms involving chronic inflammation, genotoxicity, metabolic dysregulation, epigenetic alterations, and immune evasion. Key cancer-associated bacteria, including Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis (ETBF), pks+Escherichia coli, and Helicobacter pylori, illustrate the mechanistic diversity of microbiota-associated carcinogenesis. Beyond cancer initiation, the gut microbiome can influence the efficacy and toxicity of anticancer therapies. In immunotherapy, specific microbial taxa and metabolites modulate antitumor immunity and immune checkpoint inhibitor (ICI) responses, while antibiotic-associated dysbiosis has been linked to poorer outcomes. In chemotherapy, microbial metabolism and microbiota-derived metabolites can alter drug efficacy and toxicity, including modulation of 5-fluorouracil (5-FU) activity. Microbiome-based biomarkers show promise for cancer detection and treatment prediction, with fecal microbial signatures, including F. nucleatum, potentially improving colorectal cancer (CRC) screening when incorporated into multimarker strategies. Therapeutic approaches aimed at restoring microbial symbiosis include fecal microbiota transplantation (FMT), which has shown preliminary potential to restore ICI responsiveness in treatment-refractory melanoma, and probiotic interventions, although clinical evidence remains limited. Emerging engineered microbial therapeutics, including tumor-targeting bacteria designed to deliver localized immunostimulatory payloads, are advancing toward clinical translation. Despite substantial progress, important challenges remain, including methodological heterogeneity, lack of standardized protocols, confounding factors, and unresolved safety concerns. Personalized strategies integrating microbial features with host characteristics and treatment context may ultimately enable more effective microbiome-based approaches to improve cancer outcomes.