Microbiota and their metabolites potentiate cancer immunotherapy: Therapeutic target or resource for small molecule drug discovery?

Increasing evidence has proved that microbiota is not only the target of small molecule drugs but also an underexplored resource for developing small molecule drugs. Meanwhile, microbiota as a critical modulator of the immune system impacts the efficacy and toxicity of cancer immunotherapy. Harnessing microbiota or developing microbiota-derived medications provide novel therapeutic strategies to overcome resistance to cancer immunotherapy and immune-related adverse events (irAEs). In this review, we elucidate how microbiota and their metabolites impact anti-tumor immunity and immunotherapy efficacy and highlight the potential of microbiota and their metabolites as a resource for small molecule drug discovery. We further overview the current landscape of clinical trials evaluating the potential effect of microbiota and their metabolites on immunotherapy outcomes, presenting future trends in the field of microbiota-based therapies. Microbiota-based therapies are promising therapeutic options to promote therapeutic efficacy and diminish the toxicity of immunotherapy.