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

作者：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 · 发表于：eLife · 年份：2023 · DOI：10.7554/elife.81858 · 被引用次数：37 · 研究领域：Muscle Physiology and Disorders、Muscle metabolism and nutrition、Adipose Tissue and Metabolism

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.