Gut microbiota and cancer therapy: mechanisms, challenges, and opportunities

Abstract

The gut microbiota, a vital component of the human microbiome, plays a central role in maintaining immune homeostasis and is increasingly recognized as a key contributor to chronic inflammatory diseases and cancer. Accumulating evidence indicates that the gut microbiome significantly influences tumor initiation, progression, and therapeutic outcomes, particularly in the context of cancer immunotherapy. This narrative review presents a comprehensive overview of the complex interactions between the gut microbiota and cancer, focusing on the molecular and cellular mechanisms by which microbial communities regulate carcinogenesis, tumor progression, and treatment response. These mechanisms include modulating host immune function, epigenetic regulation, maintaining intestinal barrier integrity, and metabolic reprogramming. In addition, this review synthesizes preclinical and clinical findings to examine how the gut microbiome influences the efficacy of immune checkpoint inhibitors, chemotherapy, and radiotherapy. It also highlights emerging microbiome-based therapeutic interventions, including probiotics, prebiotics, fecal microbiota transplantation (FMT), and engineered microbial therapeutics, which offer promising opportunities to enhance therapeutic efficacy, reduce treatment-related toxicity, and overcome drug resistance. Nevertheless, several important challenges must be addressed before these approaches can be widely implemented, including strain-specific variability, safety concerns in immunocompromised patients, optimizing donor selection for FMT, and developing standardized regulatory guidelines. Recent advances have further strengthened the role of microbiome-derived biomarkers and multi-omics technologies in precision oncology, enabling more accurate patient stratification and individualized treatment strategies. Moreover, artificial intelligence-driven analytical approaches are improving predictions of therapeutic responses and enabling real-time monitoring of dynamic changes in the gut microbiome during treatment. Collectively, these developments highlight the considerable potential of the gut microbiome as a therapeutic target for cancer prevention and management, with the promise of improving clinical outcomes and extending patient survival. However, translating microbiome-based interventions into routine clinical practice will require large-scale, well-designed clinical trials, standardized methodologies, and robust validation of their safety and efficacy.