肠道微生物精氨酸代谢的改变决定了骨机械适应，这一成果由第四军医大学罗卓荆等人经过不懈努力而取得。该研究于2024年5月7日发表于国际一流学术期刊《细胞—代谢》杂志上。

该研究组发现肠道微生物的消耗显著降低了骨骼对机械负荷的适应性。在实验小鼠中，小组观察到对运动有高反应和低反应的小鼠在肠道微生物组成方面的差异，其中毛螺菌科的丰度差异导致了骨机械反应性的差异。L-瓜氨酸的微生物产生及其向L-精氨酸的转化被认为是骨机械适应的关键调节因子，这些代谢物的管理增强了正常、衰老和去卵巢小鼠的骨机械反应性。

从机制上讲，L-精氨酸介导的骨机械适应性增强主要归因于骨细胞中一氧化氮-钙正反馈回路的激活。本研究确定了一种有前途的抗骨质疏松策略，通过微生物群代谢轴最大化机械负荷诱导的骨骼益处。

研究人员表示，尽管机械负荷对于维持骨骼健康和对抗骨质疏松症是必不可少的，但其实际应用在很大程度上受到骨机械反应性的高度可变性的限制。

附：英文原文

Title: Gut microbial alterations in arginine metabolism determine bone mechanical adaptation

Author: Dan Wang, Jing Cai, Qilin Pei, Zedong Yan, Feng Zhu, Zhe Zhao, Ruobing Liu, Xiangyang Guo, Tao Sun, Juan Liu, Yulan Tian, Hongbo Liu, Xi Shao, Jinghui Huang, Xiaoxia Hao, Qi Chang, Zhuojing Luo, Da Jing

Issue&Volume: 2024-05-07

Abstract: Although mechanical loading is essential for maintaining bone health and combatingosteoporosis, its practical application is limited to a large extent by the high variabilityin bone mechanoresponsiveness. Here, we found that gut microbial depletion promoteda significant reduction in skeletal adaptation to mechanical loading. Among experimentalmice, we observed differences between those with high and low responses to exercisewith respect to the gut microbial composition, in which the differential abundanceof Lachnospiraceae contributed to the differences in bone mechanoresponsiveness. Microbial productionof L-citrulline and its conversion into L-arginine were identified as key regulatorsof bone mechanoadaptation, and administration of these metabolites enhanced bone mechanoresponsivenessin normal, aged, and ovariectomized mice. Mechanistically, L-arginine-mediated enhancementof bone mechanoadaptation was primarily attributable to the activation of a nitric-oxide-calciumpositive feedback loop in osteocytes. This study identifies a promising anti-osteoporoticstrategy for maximizing mechanical loading-induced skeletal benefits via the microbiota-metaboliteaxis.

DOI: 10.1016/j.cmet.2024.04.004

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00124-4