Hao Xiaoxia, Shang Xingru, Zhang Yiwen, Hou Wenjie, Chi Ruimin, Pan Chunran, Liu Jiawei, Deng Xiaofeng, Zhang Jiaming, Xu Tao
Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Rehabilitation, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400015, China.
Metabolites. 2025 May 20;15(5):341. doi: 10.3390/metabo15050341.
The aim of this work is to investigate the impact of exercise on gut microbiome composition, serum metabolites, and their correlation with osteoarthritis (OA) severity. Thirty-six Sprague-Dawley (SD) rats were randomly divided into four groups: Sham rats without treadmill walking (Sham/Sed group, = 9), Sham rats with treadmill walking 2 months (Sham/TW2M group, = 9), PTOA rats without treadmill walking (PTOA/Sed group, = 9), and PTOA rats with treadmill walking 2 months (PTOA/TW2M group, = 9). The PTOA model was induced by transection of the anterior cruciate ligament (ACLT) and destabilization of the medial meniscus (DMM). Histological evaluation and micro-CT analysis were performed to observe the pathological changes in cartilage and subchondral bone, respectively. Additionally, we conducted 16S rDNA sequencing of fecal samples and untargeted metabolomic analysis using liquid chromatography-mass spectrometry (LC-MS) of serum samples to detect the alteration of gut microbiota composition and metabolites. Exercise effectively mitigated OA-related pathological changes, including articular cartilage degeneration and subchondral bone loss. Moreover, 16S rDNA sequencing analysis of gut microbiome revealed a decreased abundance of ( < 0.01), ( < 0.01), ( < 0.01), [] ( < 0.01), and ( < 0.01) but an increase in ( < 0.01) in PTOA/TW2M group rats compared with PTOA/Sed group as a response to exercise. In addition, the results of metabolomics analysis showed that exercise treatment contributed to the upregulation of Daidzein and Anthranilic acid and downregulation of 1-Palmitoyllysophosphatidylcholine. Moreover, the correlation analysis showed that significantly positively correlated with both OARSI (r = 0.81, < 0.01) and Mankin score (r = 0.83, < 0.01) and negatively correlated with the serum level of Anthranilic acid (r = -0.56, < 0.01) and Daidzein (r = -0.46, < 0.01). Exercise can effectively mitigate OA through slowing down articular cartilage degeneration and subchondral bone loss, modulating gut microbiota composition, and increasing beneficial metabolites.
本研究旨在探讨运动对肠道微生物群组成、血清代谢物的影响及其与骨关节炎（OA）严重程度的相关性。将36只Sprague-Dawley（SD）大鼠随机分为四组：不进行跑步机行走的假手术大鼠（假手术/静息组，n = 9）、进行2个月跑步机行走的假手术大鼠（假手术/TW2M组，n = 9）、不进行跑步机行走的髌股关节炎（PTOA）大鼠（PTOA/静息组，n = 9）和进行2个月跑步机行走的PTOA大鼠（PTOA/TW2M组，n = 9）。通过切断前交叉韧带（ACLT）和内侧半月板失稳（DMM）诱导PTOA模型。分别进行组织学评估和显微CT分析，以观察软骨和软骨下骨的病理变化。此外，我们对粪便样本进行16S rDNA测序，并使用血清样本的液相色谱-质谱联用（LC-MS）进行非靶向代谢组学分析，以检测肠道微生物群组成和代谢物的变化。运动有效减轻了OA相关的病理变化，包括关节软骨退变和软骨下骨丢失。此外，肠道微生物群的16S rDNA测序分析显示，与PTOA/静息组相比，PTOA/TW2M组大鼠中[具体菌名1]（P < 0.01）、[具体菌名2]（P < 0.01）、[具体菌名3]（P < 0.01）、[具体菌名4]（P < 0.01）和[具体菌名5]（P < 0.01）的丰度降低，但[具体菌名6]（P < 0.01）增加，这是运动的反应。此外，代谢组学分析结果表明，运动治疗有助于大豆苷元和邻氨基苯甲酸的上调以及1-棕榈酰溶血磷脂酰胆碱的下调。此外，相关性分析显示，[具体指标]与OARSI评分（r = 0.81，P < 0.01）和Mankin评分（r = 0.83，P < 0.01）均呈显著正相关，与血清邻氨基苯甲酸水平（r = -0.56，P < 0.01）和大豆苷元水平（r = -0.46，P < 0.01）呈负相关。运动可通过减缓关节软骨退变和软骨下骨丢失、调节肠道微生物群组成以及增加有益代谢物来有效减轻OA。
