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 (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.

• Authors: Zhao-Bo Luo, Shengzhong Han, Xi-Jun Yin, Hongye Liu, Junxia Wang, Meifu Xuan, Chunyun Hao, Danqi Wang, Yize Liu, Shuangyan Chang, Dongxu Li, Kai Gao, Huiling Li, Biaohu Quan, Lin-Hu Quan, Jin-Dan Kang
• Journal: eLife (Elife) Vol. 12 (04 11 2023) ISSN: 2050-084X [Electronic] England
• PMID: 37039469 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023, Luo, Han, Yin et al.

Chemical References

• Myostatin

Topics

• Animals
• Mice
• Swine
• Fecal Microbiota Transplantation
• Myostatin (genetics, metabolism)
• Muscle, Skeletal (metabolism)