OBJECTIVE To examine whether gut microbes were associated with postsurgery-sustained knee pain in patients with knee osteoarthritis (OA) by a gut microbiomics approach. METHODS Patients receiving total knee replacement (TKR) because of primary knee OA were recruited. Sustained knee pain status at ≥ 1 year after TKR was defined by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Fasting plasma and fecal samples were collected. Metabolomic profiling was performed on fasting plasma. 16S rRNA sequencing was performed on fecal samples to determine microbial composition. RESULTS Twenty patients with TKR because of primary knee OA were included in the study, with 10 experiencing sustained postsurgery pain and 10 without such pain. Age, sex, and BMI (kg/m2) were matched. Linear discriminant analysis of microbiome data identified 13 bacterial taxa that were highly abundant in the pain group and 5 that were highly abundant in the nonpain group (P < 0.05 for all). Plasma metabolomic profiling measured 622 metabolites. The correlation analysis indicated the 18 taxa were significantly correlated with 231 metabolites (P < 0.05 for all). Sparse partial least squares discriminant analysis showed that 30/231 metabolites explained 29% of total variance and can be used to clearly separate patients with sustained knee pain from patients in the nonpain group. Pathway enrichment analysis showed that these significant metabolites were enriched in the arachidonic acid metabolic pathway, bile acid biosynthesis, and linoleic acid metabolism. CONCLUSION Gut microbes may play a significant role in sustained knee pain in patients with knee OA after TKR, potentially through their activation of inflammatory pathways, lipid metabolism, and central sensitization.

中文翻译：

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膝骨关节炎患者持续膝关节疼痛的肠道微生物组学。


目的 通过肠道微生物组学方法检查肠道微生物是否与膝骨关节炎 （OA） 患者术后持续膝关节疼痛相关。方法 招募因原发性膝关节 OA 接受全膝关节置换术 （TKR） 的患者。TKR 后 ≥ 1 年的持续膝关节疼痛状态由西安大略大学和麦克马斯特大学骨关节炎指数 （WOMAC） 定义。收集空腹血浆和粪便样本。对空腹血浆进行代谢组学分析。对粪便样本进行 16S rRNA 测序以确定微生物组成。结果 20 例原发性膝关节 OA 引起的 TKR 患者被纳入研究，其中 10 例出现持续的术后疼痛，10 例没有这种疼痛。年龄、性别和 BMI （kg/m2） 匹配。微生物组数据的线性判别分析确定了 13 个细菌类群在疼痛组中高度丰富，5 个细菌类群在非疼痛组中高度丰富 （P < 0.05）。血浆代谢组学分析测量了 622 种代谢物。相关性分析表明，18 个分类群与 231 种代谢物显著相关 （P < 0.05）。稀疏偏最小二乘判别分析显示，30/231 代谢物解释了 29% 的总方差，可用于清楚地区分持续膝关节疼痛患者和非疼痛组患者。通路富集分析表明，这些显著代谢物富集于花生四烯酸代谢途径、胆汁酸生物合成和亚油酸代谢。结论肠道微生物可能在 TKR 后膝关节 OA 患者持续膝关节疼痛中发挥重要作用，可能通过激活炎症途径、脂质代谢和中枢敏化。