Multiomic analysis of different horse breeds reveals that gut microbial butyrate enhances racehorse athletic performance

Gut microbes play a vital role in host physiology, but whether specific bacterial functions contribute to the exceptional athletic performance of racehorses needs to be better understood. Here, we identify an association of gut butyrate-producing bacteria with athletic performance in racehorses (Thoroughbred horse). Butyrate-producing bacteria and microbial butyrate synthesis genes were significantly enriched in the racehorse gut, and the GC-MS results confirmed this conclusion. Using a mouse model, we demonstrated that sodium butyrate is sufficient to increase treadmill run time performance. We also show that butyrate improves the host response to exercise, significantly altering muscle fibre type in skeletal muscle, and increasing muscle mitochondrial function and activity. In addition, in-depth analysis of the published data showed that the gene for the synthesis of butyrate was also significantly enriched in the gut microbes of human athletes. Overall, our study indicates that gut microbial butyrate improves run time via the gut-muscle axis, providing novel insights into gut microbial functions and paving the way for improving athletic performance by targeted gut microbiome manipulation.