Researchers at the UMR DMEM and their colleagues have shown that the intestinal microbiota is decisive for optimal muscle function. These results open up new avenues of research to restore this function when it is impaired (aging, diabetes, excessive sedentary life, myopathies...) but also to improve sporting performance. These results were published in the American Journal of Physiology Endocrinology & Metabolism.
Our muscles are essential to maintain our posture, move or simply breathe. Severe muscle dysfunction (loss of mass) is often associated with diseases such as cancer or diabetes; it also affects the elderly or people in hypoactive situations. These muscle alterations have a considerable impact on the health of the subjects. In order to counter them, it is important to better understand muscle physiology, particularly in its relationship with other organs. In addition, the intestinal microbiota, a community of microorganisms that reside or pass through our digestive tract, now appears as a true rich and complex organ with new emerging functions. Thus the intestinal microbiota influences the function of organs such as the brain and liver and would have an impact on many diseases including cancer, Alzheimer's disease and diabetes. Is there also a functional link between the intestinal microbiota and skeletal muscle?
Genesis of the research project
The idea of testing this hypothesis of a dialogue between intestinal microbiota and skeletal muscle was born from exchanges between researchers from the DMEM unit (Montpellier) specialized in skeletal muscle and those from the MICALIS unit (Jouy en Josas) specialized in the study of intestinal microbiota during the AlimH department meetings in 2014. Most of the data published so far were mainly based on correlations between intestinal microbiota signatures and certain muscle diseases, but the causal link remained to be established. Thanks to an incentive credit from the ALIMH department in 2015 and a thesis grant on the project at DMEM in 2016, the two teams conducted experiments to analyze in mice the effects of intestinal microbiota modulation on muscle function between 2016 and the end of 2018. The complete elimination of the intestinal microbiota in mice was achieved by a 10-day broad-spectrum antibiotic treatment. Then for the next 10 days, either treatment is continued to maintain the absence of flora or the intestinal microbiota is restored by natural reseeding. Subsequently, physiological endurance running tests in mice, muscle contractility studies and numerous biological measurements were performed and analyzed at the DMEM unit, while characterizations and monitoring of the composition of the mouse microbiota were conducted by MICALIS.
The results show that the intestinal microbiota plays a decisive role in the optimal functioning of skeletal muscles. Indeed, in the absence of a microbiota, muscle function is impaired (running performance in reduced endurance, increased muscle fatigability). Further analyses indicate that changes in glucose metabolism are one of the mechanisms involved in the relationship between intestinal microbiota and muscle function. Thus, the level of glycogen, which constitutes an essential energy storage for proper muscle function, is significantly reduced in mice without intestinal microbiota. Importantly, all these observed muscle dysfunctions are corrected in mice after restoration of an intestinal microbiota by natural reseeding.
The objective of the DMEM team is now to identify the chemical mediators responsible for the effects of the intestinal microbiota on muscle function. In addition, the work undertaken aims to extend the link established between intestinal microbiota and skeletal muscle to other relevant models (hyper-muscular mice, muscular dystrophy mice) and also in humans in targeted populations (healthy volunteers in hypoactivity, high-level athletes, etc.). This research ultimately opens up new avenues for therapeutic intervention (use of symbiotics) to improve muscle function in a minimally invasive way by playing on the intestinal microbiota.
- Bénédicte Goustard Unité mixte de recherche Dynamique musculaire et métabolisme DMEM – (Inra, Université de Montpellier) Montpellier
- Christelle Ramonaxto Unité mixte de recherche Dynamique musculaire et métabolisme DMEM – (Inra, Université de Montpellier) Montpellier
Gut bacteria are critical for optimal muscle function: a potential link with glucose homeostasis.
Nay K, Jollet M, Goustard B, Baati N, Vernus B, Pontones M, Lefeuvre-Orfila L, Bendavid C, Rué O, Mariadassou M, Bonnieu A, Ollendorff V, Lepage P, Derbré F, Koechlin-Ramonatxo C.
Am J Physiol Endocrinol Metab. 2019 Jul 1;317(1):E158-E171.
doi: 10.1152/ajpendo.00521.2018. Epub 2019 Apr 30. PMID:31039010
Partners and funding
Partners involved in the project
- Unité mixte de recherche Dynamique musculaire et métabolisme DMEM – (Inra, Université de Montpellier) Montpellier,
- Institut MICALIS, unité mixte de recherche Microrobiologie de l'alimentation au service de la Santé (Micalis Institute, Inra, AgroParisTech, Université Paris-Saclay), Jouy-en-Josas,
- Laboratoire Mouvement, Sport, Santé (M2S), Université de Rennes,
- MEDES (clinique spatiale de Toulouse),
- Unité propre de recherche Mathématiques et informatique appliquées du génome à l'environnement (MAIAGE) (Inra, Université Paris-Saclay) Jouy-en-Josas
- ANSSD incentive credit for the Food Department (2015)
- CNES credit in 2017 and 2018 for the "microbiota and hypoactivity" program
- Thesis grants (INRA, Brittany Region, MENRT)