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.
Data availability
The raw reads of 16s rRNA gene sequences have been submitted to the NCBI BioSample database (Porcine data: PRJNA743164; Mice data: PRJNA743401).
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pig gut metagenome Raw sequence readsNCBI BioProject, PRJNA743164.
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mice gut metagenome Raw sequence readsNCBI BioProject, PRJNA743401.
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Original data of Luo et alScience Data Bank, doi:10.57760/sciencedb.06767.
Article and author information
Author details
Funding
National Natural Science Foundation of China (32260817)
- Jin-Dan Kang
National Natural Science Foundation of China (32260026)
- Lin-Hu Quan
Changbai Mountain Talent Project of Jilin Province (000007)
- Lin-Hu Quan
Higher Education Discipline Innovation Project (D18012)
- Lin-Hu Quan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Aleksandar D. Kostic, Joslin Diabetes Center, United States
Ethics
Animal experimentation: The animal study was approved by the Ethics Committee of Yanbian University (approval number SYXK2020-0009).
Version history
- Received: July 13, 2022
- Preprint posted: July 25, 2022 (view preprint)
- Accepted: April 6, 2023
- Accepted Manuscript published: April 11, 2023 (version 1)
- Version of Record published: April 21, 2023 (version 2)
Copyright
© 2023, Luo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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