Objective

The objective of this exploratory study was to determine if perturbations in gut microbial composition and the gut metabolome could be linked to individuals with obesity and osteoarthritis (OA).

Methods

Fecal samples were collected from obese individuals diagnosed with radiographic hand plus knee OA (n = 59), defined as involvement of at least 3 joints across both hands, and a Kellgren–Lawrence (KL) grade 2–4 (or total knee replacement) in at least one knee. Controls (n = 33) were without hand OA and with KL grade 0–1 knees. Fecal metabolomes were analyzed by a UHPLC/Q Exactive HFx mass spectrometer. Microbiome composition was determined in fecal samples by 16 S ribosomal RNA amplicon sequencing (rRNA-seq). Stepwise logistic regression models were built to determine microbiome and/or metabolic characteristics of OA.

Results

Untargeted metabolomics analysis indicated that OA cases had significantly higher levels of di- and tripeptides and significant perturbations in microbial metabolites including propionic acid, indoles, and other tryptophan metabolites. Pathway analysis revealed several significantly perturbed pathways associated with OA including leukotriene metabolism, amino acid metabolism and fatty acid utilization. Logistic regression models selected metabolites associated with the gut microbiota and leaky gut syndrome as significant predictors of OA status, particularly when combined with the rRNA-seq data.

Conclusions

Adults with obesity and knee plus hand OA have distinct fecal metabolomes characterized by increased products of proteolysis, perturbations in leukotriene metabolism, and changes in microbial metabolites compared with controls. These metabolic perturbations indicate a possible role of dysregulated proteolysis in OA.

中文翻译：

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粪便代谢组学揭示肥胖相关骨关节炎中蛋白水解失调和微生物代谢改变的产物

客观的

这项探索性研究的目的是确定肠道微生物组成和肠道代谢组的扰动是否与肥胖和骨关节炎 (OA) 患者有关。

方法

粪便样本是从被诊断为手加膝 OA 的肥胖个体（n  = 59）收集的，定义为双手至少有 3 个关节受累，并且 Kellgren–Lawrence (KL) 2-4 级（或全膝关节置换）至少在一个膝盖上。对照组 ( n  = 33) 没有手 OA 和 KL 0-1 级膝盖。通过 UHPLC/Q Exactive HFx 质谱仪分析粪便代谢组。通过 16 S 核糖体 RNA 扩增子测序 (rRNA-seq) 确定粪便样本中的微生物组组成。建立逐步逻辑回归模型以确定 OA 的微生物组和/或代谢特征。

结果

非靶向代谢组学分析表明，OA 病例的二肽和三肽水平显着升高，微生物代谢物（包括丙酸、吲哚和其他色氨酸代谢物）发生显着扰动。通路分析揭示了与 OA 相关的几个显着扰动的通路，包括白三烯代谢、氨基酸代谢和脂肪酸利用。逻辑回归模型选择与肠道微生物群和漏肠综合征相关的代谢物作为 OA 状态的重要预测因子，尤其是与 rRNA-seq 数据结合使用时。

结论

患有肥胖症和膝加手部 OA 的成年人具有明显的粪便代谢组，其特征是与对照组相比，蛋白水解产物增加、白三烯代谢紊乱以及微生物代谢物发生变化。这些代谢扰动表明蛋白水解失调可能在 OA 中发挥作用。