Microbial-Derived Exerkines as a Model of Drug Discovery

There has been a growing interest in the utilization of the gut microbiome as a therapeutic tool. The relationship between the gut microbiome and exercise provides a unique opportunity to maximize the therapeutic capacity of the gut microbiome. Here, we summarize the potential of leveraging the gut microbiome to confer the health benefits of exercise through a novel class of microbial metabolites termed microbial-derived exerkines (MDEs). We identify multiple candidate and established MDEs described in the literature (e.g., pipecolic acid, succinate, short-chain fatty acids, indole-3-propionic acid, 3-hydroxyphenylacetic acid) and explore their implications in conditions such as inflammatory bowel disease, aging, skeletal muscle atrophy, cancer, diabetes, cardiovascular disease, and Alzheimer's disease. Given the beneficial effects of exercise on numerous diseases, we anticipate MDEs will be a productive avenue for drug discovery and therapeutic progress.