Gut Microbiota-Derived Metabolites in Cancer Immunotherapy: Mechanisms and Clinical Potential

School of Medical Sciences, The University of Manchester, Manchester M13 9PL, United Kingdom

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Abstract

The human gut microbiota plays a critical role in host physiology, particularly in immune regulation and cancer progression. Notably, gut microbiota-derived metabolites have emerged as crucial regulators of anti-tumor immunity and immunotherapy efficacy. This review synthesizes recent findings on how microbial metabolites, such as short-chain fatty acids (SCFAs), bile acid derivatives, and tryptophan metabolites, interact with immune cells and signaling pathways to influence cancer immunotherapy outcomes. In terms of mechanism, they coordinate innate and adaptive immune processes, reshape the tumor microenvironment, and may enhance the anti-tumor effect. In clinical practice, interventions such as fecal microbiota transplantation (FMT), probiotic supplementation and metabolite supplementation have shown the potential to improve the response rate of treatment. However, there are still many challenges. Differences between individuals, unresolved long-term safety issues, and the complexity of the interaction between the microbiota and the immune system all hinder progress in this area. A comprehensive clarification of these mechanisms is crucial to the rational design of microbial interventions aimed at improving the effectiveness of cancer immunotherapy.