Microbial metabolites and immunotherapy: Basic rationale and clinical indications

Our microbiota has a critical role in shaping host immunity. Microbes that reside in the gut harbor a large metabolic arsenal to aid in physiological functions of the host. Microbial metabolites, which are products of microbial metabolism, such as short chain fatty acids (SCFA), purine metabolites, cyclic dinucleotides, tryptophan derivatives, and secondary bile acids, can tailor the host immune cell landscape in homeostasis and during cancer immunotherapy. The critical role of the microbiome in aiding immune checkpoint blockade therapies has become clearer over the past few years, with the most recent studies providing more detailed mechanistic insight on how microbes and their metabolites control the outcome of immunotherapy. This review summarizes recent studies on how microbial metabolites orchestrate immune responses during cancer immunotherapies.