eLife (Apr 2023)

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

  • 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

DOI
https://doi.org/10.7554/eLife.81858
Journal volume & issue
Vol. 12

Abstract

Read online

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.

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