Objectives Emerging evidence suggests that the microbiome plays an important role in the pathogenesis of osteoarthritis (OA). We aimed to test the two-hit model of OA pathogenesis and potentiation in which one ‘hit’ is provided by an adverse gut microbiome that activates innate immunity; the other ‘hit’ is underlying joint damage. Methods Medical history, faecal and blood samples were collected from human healthy controls (OA-METS-, n=4), knee OA without metabolic syndrome (OA+METS-, n=7) and knee OA with metabolic syndrome (OA+METS+, n=9). Each group of human faecal samples, whose microbial composition was identified by 16S rRNA sequencing, was pooled and transplanted into germ-free mice 2 weeks prior to meniscal/ligamentous injury (MLI) (n≥6 per group). Eight weeks after MLI, mice were evaluated for histological OA severity and synovitis, systemic inflammation and gut permeability. Results Histological OA severity following MLI was minimal in germ-free mice. Compared with the other groups, transplantation with the OA+METS+ microbiome was associated with higher mean systemic concentrations of inflammatory biomarkers (interleukin-1β, interleukin-6 and macrophage inflammatory protein-1α), higher gut permeability and worse OA severity. A greater abundance of Fusobacterium and Faecalibaterium and lesser abundance of Ruminococcaceae in transplanted mice were consistently correlated with OA severity and systemic biomarkers concentrations. Conclusion The study clearly establishes a direct gut microbiome-OA connection that sets the stage for a new means of exploring OA pathogenesis and potentially new OA therapeutics. Alterations of Fusobacterium, Faecalibaterium and Ruminococcaceae suggest a role of these particular microbes in exacerbating OA.

中文翻译：

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来自代谢受损的人类捐赠者的粪便微生物群移植会加速小鼠的骨关节炎


目标 新证据表明微生物组在骨关节炎 (OA) 的发病机制中发挥着重要作用。我们的目的是测试 OA 发病机制和增强的两次打击模型，其中一次“打击”是由激活先天免疫的不良肠道微生物组提供的；另一个“打击”是潜在的关节损伤。方法 采集健康对照者（OA-METS-，n=4）、不伴有代谢综合征的膝关节骨关节炎（OA+METS-，n=7）和伴有代谢综合征的膝关节骨关节炎（OA+METS+）的病史、粪便和血液样本。 ，n=9)。通过 16S rRNA 测序鉴定了每组人类粪便样本的微生物组成，在半月板/韧带损伤 (MLI) 前 2 周将其合并并移植到无菌小鼠体内（每组 n ≥ 6 只）。 MLI 后八周，对小鼠的组织学 OA 严重程度、滑膜炎、全身炎症和肠道通透性进行评估。结果 在无菌小鼠中，MLI 后的组织学 OA 严重程度最低。与其他组相比，移植 OA+METS+ 微生物群与炎症生物标志物（白细胞介素-1β、白细胞介素-6 和巨噬细胞炎症蛋白-1α）的平均全身浓度较高、肠道通透性较高和 OA 严重程度较差相关。移植小鼠中梭杆菌属和 Faecalibaterium 丰度较高，瘤胃球菌科丰度较低，与 OA 严重程度和全身生物标志物浓度一致相关。结论 该研究明确建立了肠道微生物组与 OA 之间的直接联系，为探索 OA 发病机制的新方法和潜在的新 OA 治疗方法奠定了基础。梭杆菌属、Faecalibaterium 和瘤胃球菌科的变化表明这些特殊微生物在加剧 OA 方面发挥了作用。