Microbial allies: Gut microbiome and immunotherapy synergies in colorectal cancer. A narrative review

Background: Colorectal cancer (CRC) remains a global health problem. It is the most common malignancy of the gastrointestinal tract, with a global incidence of over 1.9 million cases, making it the third most common cause of cancer-related deaths worldwide. The incidence is increasing particularly in low- and middle-income countries and among individuals under 50 years of age, with lifestyle and environmental factors contributing to this trend-many of which affect the gut microbiome. Main body: Advances in CRC treatment have introduced immunotherapy, particularly for tumours with mismatch repair deficiency (dMMR) and high microsatellite instability (MSI-H). This review explores the symbiotic relationship between the gut microbiome and immunotherapy in CRC. The human colon harbours a complex microbiome composed of diverse microbial species and vast genetic diversity, with structural, metabolic, and immunomodulatory functions. Dysbiosis, influenced by factors such as diet and lifestyle, contributes to CRC pathogenesis through inflammation and metabolic disruptions. Immunotherapy, specifically immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment by enhancing T cell-mediated immune responses against cancer cells. In CRC, ICIs have demonstrated efficacy in MSI-H/dMMR tumours that represent less than 15% of all CRC cases. Challenges persist in treating microsatellite stable (MSS) CRC in regard to immunotherapy. Emerging evidence suggests that specific gut microbiota compositions influence the response to ICIs by modulating systemic immune responses and tumour microenvironments, potentially having a key role for MSS CRC patients. Strategies to manipulate the gut microbiome, including probiotics and faecal microbiota transplantation, hold promise in augmenting immunotherapy efficacy. Conclusion: The review underscores the potential of the gut microbiome as a predictive biomarker and therapeutic target in CRC immunotherapy. Ultimately, harnessing the therapeutic potential of the gut microbiome represents a promising avenue for enhancing immunotherapy outcomes and advancing personalized medicine in CRC care.