The Role of Microbiota-Derived Vitamins in Immune Homeostasis and Enhancing Cancer Immunotherapy

SIMPLE SUMMARY: Despite clinical success, only a limited percentage of cancer patients are responsive to immunotherapy. Recently, gut microbiota modulation has been suggested as a tool to enhance immunotherapy efficacy, and mechanisms for these effects may be linked to microbial contributions—such as microbial-derived vitamins—to immune responses. While humans can acquire their vitamins from dietary sources, gut microbial-derived vitamins are crucial to the immune system’s function. The production of these vitamins can be altered by the bidirectional crosstalk between the immune system and the gut microbiome; however, their exact mechanism of action in bacterial communities and immune responses remains elusive. Further studies and clinical trials are needed to understand the role of microbial-derived vitamins in anti-tumor immune responses and their role in the efficacy of immunotherapies. This review will discuss the in-depth mechanisms of selective vitamins and their role in modulating immune responses, as well as their potential as immunotherapy enhancers. ABSTRACT: Not all cancer patients who receive immunotherapy respond positively and emerging evidence suggests that the gut microbiota may be linked to treatment efficacy. Though mechanisms of microbial contributions to the immune response have been postulated, one likely function is the supply of basic co-factors to the host including selected vitamins. Bacteria, fungi, and plants can produce their own vitamins, whereas humans primarily obtain vitamins from exogenous sources, yet despite the significance of microbial-derived vitamins as crucial immune system modulators, the microbiota is an overlooked source of these nutrients in humans. Microbial-derived vitamins are often shared by gut bacteria, stabilizing bioenergetic pathways amongst microbial communities. Compositional changes in gut microbiota can affect metabolic pathways that alter immune function. Similarly, the immune system plays a pivotal role in maintaining the gut microbiota, which parenthetically affects vitamin biosynthesis. Here we elucidate the immune-interactive mechanisms underlying the effects of these microbially derived vitamins and how they can potentially enhance the activity of immunotherapies in cancer.