Data_Sheet_1_Hypoxia Improves Endurance Performance by Enhancing Short Chain Fatty Acids Production via Gut Microbiota Remodeling.PDF

Hypoxia environment has been widely used to promote exercise capacity. However, the underlying mechanisms still need to be further elucidated. In this study, mice were exposed to the normoxia environment (21% O2) or hypoxia environment (16.4% O2) for 4 weeks. Hypoxia-induced gut microbiota remodeling characterized by the increased abundance of Akkermansia and Bacteroidetes genera, and their related short-chain fatty acids (SCFAs) production. It was observed that hypoxia markedly improved endurance by significantly prolonging the exhaustive running time, promoting mitochondrial biogenesis, and ameliorating exercise fatigue biochemical parameters, including urea nitrogen, creatine kinase, and lactic acid, which were correlated with the concentrations of SCFAs. Additionally, the antibiotics experiment partially inhibited hypoxia-induced mitochondrial synthesis. The microbiota transplantation experiment demonstrated that the enhancement of endurance capacity induced by hypoxia was transferable, indicating that the beneficial effects of hypoxia on exercise performance were partly dependent on the gut microbiota. We further identified that acetate and butyrate, but not propionate, stimulated mitochondrial biogenesis and promoted endurance performance. Our results suggested that hypoxia exposure promoted endurance capacity partially by the increased production of SCFAs derived from gut microbiota remodeling.

缺氧环境已被广泛用于促进运动能力。然而，其潜在的机制仍有待进一步阐明。在本研究中，小鼠被暴露于常氧环境（21%的氧气浓度）或缺氧环境（16.4%的氧气浓度）共4周。缺氧诱导的肠道菌群重塑表现为阿克曼氏菌属和拟杆菌属丰度的增加及其相关短链脂肪酸（SCFAs）的产生。观察发现，缺氧显著提高了耐力，通过显著延长耗竭性跑步时间、促进线粒体生物发生以及改善运动疲劳的生化参数（包括尿素氮、肌酸激酶和乳酸）来实现，这些参数与SCFAs的浓度相关。此外，抗生素实验部分抑制了缺氧诱导的线粒体合成。肠道菌群移植实验表明，由缺氧诱导的耐力提升具有可转移性，这表明缺氧对运动表现的有益影响部分依赖于肠道菌群。我们进一步发现，乙酸和丁酸，而非丙酸，刺激线粒体生物发生并促进耐力表现。我们的结果表明，缺氧暴露通过增加肠道菌群重塑产生的SCFAs的产生，部分促进了耐力能力的提升。