Ran Cong, Xu Yuanze, Wang Qinyue, Cao Hong, Li Dan, Wang Yingyu, Yan Ji'ai, Yang Ju, Sun Jing, Liu Yiran, Xia Yanping, Zhang Liujing, Wang Xuesong, Zhang Feng
Department of Nutrition, Affiliated Hospital of Jiangnan University, Wuxi, 214122, Jiangsu, China; Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu, China.
The Second Clinical College, Zhejiang Chinese Medical University, Hangzhou, 310009, China.
Microb Pathog. 2025 Oct;207:107911. doi: 10.1016/j.micpath.2025.107911. Epub 2025 Jul 17.
Although obesity is recognized as a mechanical driver of osteoarthritis (OA), emerging evidence suggests gut microbiota independently contributes to OA pathogenesis. OA develops even in individuals without obesity, yet the distinct mechanistic roles of gut microbiota in OA progression among hosts with and without obesity remain uncharacterized. OA can develop in individuals without obesity, yet the distinct roles of gut microbiota in OA progression among those with and without obesity remain unclear. This study directly compares how gut microbiota differentially modulates OA development in these two populations.
Twenty-five SD rats underwent anterior cruciate ligament transection (ACLT), gut microbiota depletion and fecal microbiota transplantation (FMT) from four types of donors: healthy controls (C), OA patients without obesity (OA), non-OA patients with obesity (OB), and OA patients with obesity (OAB). Five rats in group SAB underwent sham surgery and received FMT from OA patients with obesity. After 8 weeks, joint histopathology, plasma cytokines, fecal Short-chain fatty acids (SCFAs), and microbiota composition were analyzed.
Rats receiving FMT from OA patients without obesity displayed the most severe cartilage degeneration and synovitis, with elevated levels of IL-6/TNF-α and acetic acid. Bacteroides acidifaciens was the dominant microbe in the OA group and correlated with both OA severity and acetic acid levels. In contrast, rats receiving FMT from patients with/without obesity (OB/OAB) exhibited enrichment of propionic acid producers, Lactobacillus and Oscillibacter, which were inversely associated with inflammation. Mechanical stress primarily drove OA in rats with obesity, whereas OA pathology in individuals without obesity was microbiota dependent.
Gut microbiota from OA patients without obesity exacerbates disease via B. acidifaciens mediated acetic acid overproduction, while the presence of obesity enriches beneficial taxa that attenuate inflammation. Mechanical load remains pivotal in OA with obesity. Targeting microbiota dysbiosis may offer novel therapeutic avenues, particularly for OA patients without obesity.
尽管肥胖被认为是骨关节炎（OA）的一个机械驱动因素，但新出现的证据表明肠道微生物群独立地促成了OA的发病机制。即使在没有肥胖的个体中也会发生OA，然而肠道微生物群在肥胖和非肥胖宿主的OA进展中所起的不同机制作用仍未得到明确。OA可在没有肥胖的个体中发生，但肠道微生物群在肥胖和非肥胖个体的OA进展中所起的不同作用仍不清楚。本研究直接比较了肠道微生物群如何在这两个人群中差异调节OA的发展。
25只SD大鼠接受前交叉韧带横断术（ACLT）、肠道微生物群清除和来自四种类型供体的粪便微生物群移植（FMT）：健康对照（C）、无肥胖的OA患者（OA）、有肥胖的非OA患者（OB）和有肥胖的OA患者（OAB）。SAB组的5只大鼠接受假手术，并接受来自有肥胖的OA患者的FMT。8周后，分析关节组织病理学、血浆细胞因子（细胞活素）、粪便短链脂肪酸（SCFAs）和微生物群组成。
接受来自无肥胖的OA患者的FMT的大鼠表现出最严重的软骨退变和滑膜炎，白细胞介素-6/肿瘤坏死因子-α水平和乙酸水平升高。嗜酸拟杆菌是OA组中的优势微生物，与OA严重程度和乙酸水平均相关。相比之下，接受来自有/无肥胖患者（OB/OAB）的FMT的大鼠表现出丙酸产生菌、乳酸杆菌和颤杆菌的富集，这些与炎症呈负相关。机械应力主要导致肥胖大鼠的OA，而无肥胖个体的OA病理则依赖于微生物群。
来自无肥胖的OA患者的肠道微生物群通过嗜酸拟杆菌介导的乙酸过量产生加剧疾病，而肥胖的存在使有益类群富集，从而减轻炎症。机械负荷在肥胖性OA中仍然至关重要。针对微生物群失调可能提供新的治疗途径，特别是对于无肥胖的OA患者。
