Fecal transplant from myostatin deletion pigs positively impacts the gut-muscle axis.

Abstract

The host genome may influence the composition of the intestinal microbiota, and the intestinal microbiota has a significant effect on muscle growth and development. In this study, we found that the deletion of the myostatin (<i>MSTN</i>) gene positively regulates the expression of the intestinal tight junction-related genes <i>TJP1</i> and <i>OCLN</i> through the myosin light-chain kinase/myosin light chain pathway. The intestinal structure of <i>MSTN^-/-</i> pigs differed from wild-type, including by the presence of a thicker muscularis and longer plicae. Together, these changes affect the structure of intestinal microbiota. Mice transplanted with the intestinal microbiota of <i>MSTN^-/-</i> pigs had myofibers with larger cross-sectional areas and higher fast-twitch glycolytic muscle mass. Microbes responsible for the production of short-chain fatty acids (SCFAs) were enriched in both the <i>MSTN^-/-</i> pigs and recipient mice, and SCFAs levels were elevated in the colon contents. We also demonstrated that valeric acid stimulates type IIb myofiber growth by activating the Akt/mTOR pathway via G protein-coupled receptor 43 and ameliorates dexamethasone-induced muscle atrophy. This is the first study to identify the <i>MSTN</i> gene-gut microbiota-SCFA axis and its regulatory role in fast-twitch glycolytic muscle growth.