Acetate and succinate benefit host muscle energetics as exercise‐associated post‐biotics

Abstract Recently, the gut microbiome has emerged as a potent modulator of exercise‐induced systemic adaptation and appears to be crucial for mediating some of the benefits of exercise. This study builds upon previous evidence establishing a gut microbiome‐skeletal muscle axis, identifying exercise‐induced changes in microbiome composition. Metagenomics sequencing of fecal samples from non‐exercise‐trained controls or exercise‐trained mice was conducted. Biodiversity indices indicated exercise training did not change alpha diversity. However, there were notable differences in beta‐diversity between trained and untrained microbiomes. Exercise significantly increased the level of the bacterial species Muribaculaceae bacterium DSM 103720 . Computation simulation of bacterial growth was used to predict metabolites that accumulate under in silico culture of exercise‐responsive bacteria. We identified acetate and succinate as potential gut microbial metabolites that are produced by Muribaculaceae bacterium , which were then administered to mice during a period of mechanical overload‐induced muscle hypertrophy. Although no differences were observed for the overall muscle growth response to succinate or acetate administration during the first 5 days of mechanical overload‐induced hypertrophy, acetate and succinate increased skeletal muscle mitochondrial respiration. When given as post‐biotics, succinate or acetate treatment may improve oxidative metabolism during muscle hypertrophy.