Multiomic analysis of racehorses identifies the role of gut microbial butyrate in enhancing athletic performance via the gut-muscle/mitochondrial axis

Gut microbes and their metabolites play a vital role in the health and host physiology, but how 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. Butyrate-producing bacteria and genes related to in butyrate synthesis were significantly enriched in the racehorse gut, and the targeted metabolomic results verified this conclusion. Supplementing butyrate in mice, we demonstrated that butyrate is sufficient to increase treadmill run time performance. We also show that butyrate improves the host response to exercise, significantly reducing inflammation in the small intestine, altering muscle fibre type in skeletal muscle, and increasing muscle mitochondrial function and activity. We also reported that the role of gut microbial butyrate might be conserved in the racehorse and human athlete. Overall, our study provides novel insights into gut microbial functions and paves the way for improving athletic performance by targeted gut microbiome manipulation.Gut microbes and their metabolites play a vital role in the health and host physiology, but how 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. Butyrate-producing bacteria and genes related to in butyrate synthesis were significantly enriched in the racehorse gut, and the targeted metabolomic results verified this conclusion. Supplementing butyrate in mice, we demonstrated that butyrate is sufficient to increase treadmill run time performance. We also show that butyrate improves the host response to exercise, significantly reducing inflammation in the small intestine, altering muscle fibre type in skeletal muscle, and increasing muscle mitochondrial function and activity. We also reported that the role of gut microbial butyrate might be conserved in the racehorse and human athlete. Overall, our study provides novel insights into gut microbial functions and paves the way for improving athletic performance by targeted gut microbiome manipulation.