Department of Neurology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China.
Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
J Parkinsons Dis. 2024;14(6):1129-1138. doi: 10.3233/JPD-240244.
In experimental and observational studies, the characteristics of gut microbiota have been associated with Parkinson's disease (PD), among which metabolic pathways played an important role. However, the causality remained unclear.
Herein, we aimed to determine the potential impact of gut microbiota and gut microbiota-derived metabolites on PD risk using a Mendelian randomization (MR) approach.
We included as exposures gut microbial taxa abundance and gut-derived metabolites (branched chain amino acids [BCAAs]), with PD as the outcome. In addition, we explored whether BCAAs act as a mediating factor in the pathway from gut microbiota to PD.
We found evidence of a causality of 15 microbial taxa and PD before and after sensitivity analyses, but not after multiple testing correction. There was significant association between BCAAs levels and the risk of PD, especially isoleucine (OR = 0.995, 95% CI 0.992-0.999, p = 0.004, pFDR = 0.012). In addition, the causality of gut microbiota and BCAAs was also explored that the increased g_Coprococcus abundance can result in the decrease in isoleucine level (OR = 1.046; 95% CI, 1.009-1.085; p = 0.016).
Our findings indicated suggestive association between gut microbiota and its metabolites and PD. Furthermore, higher BCAAs levels were associated with the decreased PD risk. This study may provide new targets for PD treatment, such as dietary BCAAs supplementation.
在实验和观察性研究中，肠道微生物群的特征与帕金森病（PD）有关，其中代谢途径起着重要作用。然而，因果关系仍不清楚。
本研究旨在通过孟德尔随机化（MR）方法，确定肠道微生物群及其衍生代谢物对 PD 风险的潜在影响。
我们将肠道微生物分类群丰度和肠道衍生代谢物（支链氨基酸[BCAAs]）作为暴露因素，以 PD 作为结局。此外，我们还探讨了 BCAAs 是否作为肠道微生物群到 PD 途径中的中介因素。
我们发现了 15 种微生物分类群与 PD 之间在进行敏感性分析前后存在因果关系，但在进行多次检验校正后则不存在。BCAAs 水平与 PD 风险之间存在显著关联，尤其是异亮氨酸（OR=0.995，95%CI 0.992-0.999，p=0.004，pFDR=0.012）。此外，我们还探讨了肠道微生物群和 BCAAs 之间的因果关系，即增加的 g_Coprococcus 丰度可导致异亮氨酸水平降低（OR=1.046；95%CI，1.009-1.085；p=0.016）。
我们的研究结果表明，肠道微生物群及其代谢物与 PD 之间存在相关性。此外，较高的 BCAAs 水平与 PD 风险降低有关。本研究为 PD 的治疗提供了新的靶点，例如饮食补充 BCAAs。
