Dysbiosis of the gut microbiome impairs mouse skeletal muscle adaptation to exercise

Taylor R. Valentino, Ivan J. Vechetti, C. Brooks Mobley, Cory M. Dungan, Lesley Golden, Jensen Goh, John J. McCarthy

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Abstract: There is emerging evidence of a gut microbiome–skeletal muscle axis. The purpose of this study was to determine if an intact gut microbiome was necessary for skeletal muscle adaptation to exercise. Forty-two 4-month-old female C57BL/6J mice were randomly assigned to untreated (U) or antibiotic-treated (T) non-running controls (CU or CT, respectively) or progressive weighted wheel running (PoWeR, P) untreated (PU) or antibiotic-treated (PT) groups. Antibiotic treatment resulted in disruption of the gut microbiome as indicated by a significant depletion of gut microbiome bacterial species in both CT and PT groups. The training stimulus was the same between PU and PT groups as assessed by weekly (12.35 ± 2.06 vs. 11.09 ± 1.76 km/week, respectively) and total (778.9 ± 130.5 vs. 703.8 ± 112.9 km, respectively) running activity. In response to PoWeR, PT showed less hypertrophy of soleus type 1 and 2a fibres and plantaris type 2b/x fibres compared to PU. The higher satellite cell and myonuclei abundance of PU plantaris muscle after PoWeR was not observed in PT. The fibre-type shift of PU plantaris muscle to a more oxidative type 2a fibre composition following PoWeR was blunted in PT. There was no difference in serum cytokine levels among all groups suggesting disruption of the gut microbiome did not induce systemic inflammation. The results of this study provide the first evidence that an intact gut microbiome is necessary for skeletal muscle adaptation to exercise. (Figure presented.). Key points: Dysbiosis of the gut microbiome caused by continuous antibiotic treatment did not affect running activity. Continuous treatment with antibiotics did not result in systemic inflammation as indicated by serum cytokine levels. Gut microbiome dysbiosis was associated with blunted fibre type-specific hypertrophy in the soleus and plantaris muscles in response to progressive weighted wheel running (PoWeR). Gut microbiome dysbiosis was associated with impaired PoWeR-induced fibre-type shift in the plantaris muscle. Gut microbiome dysbiosis was associated with a loss of PoWeR-induced myonuclei accretion in the plantaris muscle.

Original languageEnglish
Pages (from-to)4845-4863
Number of pages19
JournalJournal of Physiology
Volume599
Issue number21
DOIs
StatePublished - Nov 1 2021

Bibliographical note

Funding Information:
This study was funded by an NIH T‐32 training grant (GM118292) awarded to T.R.V. and an NIH R21 (AG071888) awarded to J.J.M.

Publisher Copyright:
© 2021 The Authors. The Journal of Physiology © 2021 The Physiological Society

Keywords

  • dysbiosis
  • exercise
  • gut microbiome
  • hypertrophy
  • skeletal muscle

ASJC Scopus subject areas

  • Physiology

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