DMEM, University of Montpellier, INRA, Montpellier , France.
Laboratory "Movement Sport and Health Sciences" EA7470, University of Rennes/ENS Rennes , France.
Am J Physiol Endocrinol Metab. 2019 Jul 1;317(1):E158-E171. doi: 10.1152/ajpendo.00521.2018. Epub 2019 Apr 30.
Gut microbiota is involved in the development of several chronic diseases, including diabetes, obesity, and cancer, through its interactions with the host organs. It has been suggested that the cross talk between gut microbiota and skeletal muscle plays a role in different pathological conditions, such as intestinal chronic inflammation and cachexia. However, it remains unclear whether gut microbiota directly influences skeletal muscle function. In this work, we studied the impact of gut microbiota modulation on mice skeletal muscle function and investigated the underlying mechanisms. We determined the consequences of gut microbiota depletion after treatment with a mixture of a broad spectrum of antibiotics for 21 days and after 10 days of natural reseeding. We found that, in gut microbiota-depleted mice, running endurance was decreased, as well as the extensor digitorum longus muscle fatigue index in an ex vivo contractile test. Importantly, the muscle endurance capacity was efficiently normalized by natural reseeding. These endurance changes were not related to variation in muscle mass, fiber typology, or mitochondrial function. However, several pertinent glucose metabolism markers, such as ileum gene expression of short fatty acid chain and glucose transporters G protein-coupled receptor 41 and sodium-glucose cotransporter 1 and muscle glycogen level, paralleled the muscle endurance changes observed after treatment with antibiotics for 21 days and reseeding. Because glycogen is a key energetic substrate for prolonged exercise, modulating its muscle availability via gut microbiota represents one potent mechanism that can contribute to the gut microbiota-skeletal muscle axis. Taken together, our results strongly support the hypothesis that gut bacteria are required for host optimal skeletal muscle function.
肠道微生物群通过与宿主器官的相互作用，参与多种慢性疾病的发生，包括糖尿病、肥胖症和癌症。有人提出，肠道微生物群与骨骼肌之间的串扰在不同的病理条件下发挥作用，如肠道慢性炎症和恶病质。然而，肠道微生物群是否直接影响骨骼肌功能仍不清楚。在这项工作中，我们研究了肠道微生物群调节对小鼠骨骼肌功能的影响，并探讨了潜在的机制。我们确定了用广谱抗生素混合物处理 21 天和自然再定植 10 天后肠道微生物群耗竭的后果。我们发现，在肠道微生物群耗竭的小鼠中，跑步耐力降低，并且在离体收缩试验中伸趾长肌疲劳指数升高。重要的是，自然再定植有效地使肌肉耐力恢复正常。这些耐力变化与肌肉质量、纤维类型或线粒体功能的变化无关。然而，一些相关的葡萄糖代谢标志物，如回肠短链脂肪酸和葡萄糖转运蛋白 G 蛋白偶联受体 41 和钠-葡萄糖协同转运蛋白 1 的基因表达以及肌肉糖原水平，与用抗生素处理 21 天和再定植后观察到的肌肉耐力变化平行。因为糖原是长时间运动的关键能量底物，通过肠道微生物群调节其肌肉可用性是一种潜在的机制，可以有助于肠道微生物群-骨骼肌轴。总之，我们的结果强烈支持这样的假设，即肠道细菌是宿主最佳骨骼肌功能所必需的。
