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).

The following data sets were generated
    1. Luo ZB
    (2022) Original data of Luo et al
    Science Data Bank, doi:10.57760/sciencedb.06767.

Article and author information

Author details

  1. Zhao-Bo Luo

    Department of Animal Science, Yanbian University, Yanji, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Shengzhong Han

    Department of Animal Science, Yanbian University, Yanji, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Xi-Jun Yin

    Department of Animal Science, Yanbian University, Yanji, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Hongye Liu

    Department of Animal Science, Yanbian University, Yanji, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Junxia Wang

    Department of Animal Science, Yanbian University, Yanji, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Meifu Xuan

    Department of Animal Science, Yanbian University, Yanji, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Chunyun Hao

    College of Integration Science, Yanbian University, Yanji, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Danqi Wang

    College of Integration Science, Yanbian University, Yanji, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0009-0001-7656-9901
  9. Yize Liu

    Key Laboratory of Natural Medicines of the Changbai Mountain, Yanbian University, Yanji, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Shuangyan Chang

    Department of Animal Science, Yanbian University, Yanji, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Dongxu Li

    College of Integration Science, Yanbian University, Yanji, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Kai Gao

    Department of Animal Science, Yanbian University, Yanji, China
    Competing interests
    The authors declare that no competing interests exist.
  13. Huiling Li

    Jilin Provincial Key Laboratory of Transgenic Animal and Embryo Engineering, Yanbian University, Yanji, China
    Competing interests
    The authors declare that no competing interests exist.
  14. Biaohu Quan

    Department of Animal Science, Yanbian University, Yanji, China
    Competing interests
    The authors declare that no competing interests exist.
  15. Lin-Hu Quan

    Key Laboratory of Natural Medicines of the Changbai Mountain, Yanbian University, Yanji, China
    For correspondence
    lhquan@ybu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7195-8078
  16. Jin-Dan Kang

    Department of Animal Science, Yanbian University, Yanji, China
    For correspondence
    jdkang@ybu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.

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

  1. 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

  1. Received: July 13, 2022
  2. Preprint posted: July 25, 2022 (view preprint)
  3. Accepted: April 6, 2023
  4. Accepted Manuscript published: April 11, 2023 (version 1)
  5. 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.

Metrics

  • 925
    Page views
  • 205
    Downloads
  • 5
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Zhao-Bo Luo
  2. Shengzhong Han
  3. Xi-Jun Yin
  4. Hongye Liu
  5. Junxia Wang
  6. Meifu Xuan
  7. Chunyun Hao
  8. Danqi Wang
  9. Yize Liu
  10. Shuangyan Chang
  11. Dongxu Li
  12. Kai Gao
  13. Huiling Li
  14. Biaohu Quan
  15. Lin-Hu Quan
  16. Jin-Dan Kang
(2023)
Fecal transplant from myostatin deletion pigs positively impacts the gut-muscle axis
eLife 12:e81858.
https://doi.org/10.7554/eLife.81858

Share this article

https://doi.org/10.7554/eLife.81858

Further reading

    1. Developmental Biology
    2. Immunology and Inflammation
    Amir Hossein Kayvanjoo, Iva Splichalova ... Elvira Mass
    Research Article Updated

    During embryogenesis, the fetal liver becomes the main hematopoietic organ, where stem and progenitor cells as well as immature and mature immune cells form an intricate cellular network. Hematopoietic stem cells (HSCs) reside in a specialized niche, which is essential for their proliferation and differentiation. However, the cellular and molecular determinants contributing to this fetal HSC niche remain largely unknown. Macrophages are the first differentiated hematopoietic cells found in the developing liver, where they are important for fetal erythropoiesis by promoting erythrocyte maturation and phagocytosing expelled nuclei. Yet, whether macrophages play a role in fetal hematopoiesis beyond serving as a niche for maturing erythroblasts remains elusive. Here, we investigate the heterogeneity of macrophage populations in the murine fetal liver to define their specific roles during hematopoiesis. Using a single-cell omics approach combined with spatial proteomics and genetic fate-mapping models, we found that fetal liver macrophages cluster into distinct yolk sac-derived subpopulations and that long-term HSCs are interacting preferentially with one of the macrophage subpopulations. Fetal livers lacking macrophages show a delay in erythropoiesis and have an increased number of granulocytes, which can be attributed to transcriptional reprogramming and altered differentiation potential of long-term HSCs. Together, our data provide a detailed map of fetal liver macrophage subpopulations and implicate macrophages as part of the fetal HSC niche.

    1. Developmental Biology
    2. Neuroscience
    Smrithi Prem, Bharati Dev ... Emanuel DiCicco-Bloom
    Research Article Updated

    Autism spectrum disorder (ASD) is defined by common behavioral characteristics, raising the possibility of shared pathogenic mechanisms. Yet, vast clinical and etiological heterogeneity suggests personalized phenotypes. Surprisingly, our iPSC studies find that six individuals from two distinct ASD subtypes, idiopathic and 16p11.2 deletion, have common reductions in neural precursor cell (NPC) neurite outgrowth and migration even though whole genome sequencing demonstrates no genetic overlap between the datasets. To identify signaling differences that may contribute to these developmental defects, an unbiased phospho-(p)-proteome screen was performed. Surprisingly despite the genetic heterogeneity, hundreds of shared p-peptides were identified between autism subtypes including the mTOR pathway. mTOR signaling alterations were confirmed in all NPCs across both ASD subtypes, and mTOR modulation rescued ASD phenotypes and reproduced autism NPC-associated phenotypes in control NPCs. Thus, our studies demonstrate that genetically distinct ASD subtypes have common defects in neurite outgrowth and migration which are driven by the shared pathogenic mechanism of mTOR signaling dysregulation.