Fecal transplant from myostatin deletion pigs positively impacts the gut-muscle axis
Zhao‐Bo Luo, Sheng‐Zhong Han, Xi‐Jun Yin, Hongye Liu, Junxia Wang, Mei‐Fu Xuan, Chunyun Hao, Danqi Wang, Yize Liu, Shuang-Yan Chang, Dongxu Li, Kai Gao, Huiling Li, Biao‐Hu Quan, Lin‐Hu Quan, Jin‐Dan Kang
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 ( MSTN ) gene positively regulates the expression of the intestinal tight junction-related genes TJP1 and OCLN through the myosin light-chain kinase/myosin light chain pathway. The intestinal structure of MSTN −/− 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 MSTN −/− 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 MSTN −/− 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 MSTN gene-gut microbiota-SCFA axis and its regulatory role in fast-twitch glycolytic muscle growth.