■在实验和观察研究中,肠道菌群的特征与帕金森病(PD)有关,其中代谢途径发挥了重要作用。然而,因果关系尚不清楚。
■这里,我们旨在使用孟德尔随机化(MR)方法确定肠道微生物群和肠道微生物群衍生的代谢物对PD风险的潜在影响.
■我们包括肠道微生物类群的丰度和肠道衍生的代谢物(支链氨基酸[BCAAs]),以PD为结果。此外,我们探讨了BCAAs是否在从肠道微生物群到PD的通路中起介导因子的作用。
■我们在敏感性分析前后发现了15个微生物类群和PD的因果关系的证据,但不是经过多次测试校正。BCAAs水平与PD的风险之间存在显着关联,尤其是异亮氨酸(OR=0.995,95%CI0.992-0.999,p=0.004,pFDR=0.012)。此外,还探讨了肠道微生物群和BCAAs的因果关系,即g_Coprococus丰度增加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产物与PD之间存在暗示性关联。此外,较高的BCAAs水平与PD风险降低相关.本研究可能为PD治疗提供新的靶点,如膳食BCAAs补充。
肠道微生物群及其代谢产物(支链氨基酸,BCAA)似乎是帕金森病(PD)的相关危险因素。到目前为止,研究主要集中在肠道微生物群及其代谢物的横断面观察研究,但本次孟德尔随机化分析评估了肠道菌群和肠道菌群衍生代谢物(BCAAs)对PD风险的潜在影响.肠道微生物群和BCAA作为暴露,PD作为结果,发现肠道菌群与PD之间没有显着相关性,在提高BCAA水平的同时,尤其是异亮氨酸,增加PD的风险。此外,我们还证明,BCAAs可以在依赖于肠道微生物群的PD中发挥作用。例如,g-coproccus丰度的增加可导致PD中异亮氨酸水平的降低。因此,在未来,通过维持肠道微生物群及其代谢产物的稳态,可以降低PD风险.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
Dysbiosis of gut microbiota and its metabolites (branched chain amino acids, BCAAs) appears to be a related risk factor for Parkinson’s disease (PD). Thus far, studies mostly focused on cross-sectional observational studies of gut microbiota and its metabolites, but this Mendelian randomization analysis evaluated the potential impact of gut microbiota and gut microbiota derived metabolites (BCAAs) on PD risk. Gut microbiota and BCAAs as exposures and PD as outcome, it was found that there was no significant correlation between gut microbiota and PD, while increasing levels of BCAAs, especially isoleucine, increased the risk of PD. In addition, we also demonstrated that BCAAs could play a role in PD relying on the gut microbiota. For example, an increase in g-Coprococcus abundance can lead to a decrease in isoleucine levels in PD. Therefore, in the future, the PD risk may be reduced by maintaining the homeostasis of gut microbiota and its metabolites.