Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
Department of Neurology, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan.
J Parkinsons Dis. 2022;12(4):1219-1230. doi: 10.3233/JPD-223179.
Emerging evidence suggests that gut dysbiosis contributes to Parkinson's disease (PD) by signaling through microbial metabolites. Hippuric acid (HA), indole derivatives, and secondary bile acids are among the most common gut metabolites.
To examine the relationship of systemic concentrations of these microbial metabolites associated with changes of gut microbiota, PD status, and severity of PD.
We enrolled 56 patients with PD and 43 age- and sex-matched healthy participants. Motor and cognitive severity were assessed with Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III motor score and the Mini-Mental State Examination (MMSE), respectively. Plasma concentrations of targeted gut metabolites were measured with liquid chromatography-tandem mass spectrometry. Gut microbiota was analyzed with shotgun metagenomic sequencing.
Compared with controls, PD patients had significantly higher plasma levels of HA, indole-3-propionic acid (IPA), deoxycholic acid (DCA), and glycodeoxycholic acid (GDCA). After adjustment for age and sex in a multivariate logistic regression analysis, plasma levels of HA (odds ratio [OR] 3.21, p < 0.001), IPA (OR 2.59, p = 0.031), and GDCA (OR 2.82, p = 0.036) were associated with positive PD status. Concentrations of these gut metabolites did not correlate with MDS-UPDRS part III score or MMSE after adjustment for confounders. Microbial metabolite levels were associated with the relative abundance of pro-inflammatory gut bacteria.
Aberrant gut microbial metabolites of HA, indole derivatives and secondary bile acids associated with specific gut microbiota changes were observed in patients with PD.
有新证据表明，肠道菌群失调通过微生物代谢产物发出信号，从而导致帕金森病（PD）。马尿酸（HA）、吲哚衍生物和次级胆汁酸是最常见的肠道代谢物之一。
研究与肠道微生物群变化、PD 状态和 PD 严重程度相关的这些微生物代谢产物的系统浓度的关系。
我们纳入了 56 名 PD 患者和 43 名年龄和性别匹配的健康参与者。使用运动障碍协会统一帕金森病评定量表（MDS-UPDRS）第三部分运动评分和简易精神状态检查（MMSE）分别评估运动和认知严重程度。使用液相色谱-串联质谱法测量靶向肠道代谢物的血浆浓度。使用 shotgun 宏基因组测序分析肠道微生物群。
与对照组相比，PD 患者的 HA、吲哚-3-丙酸（IPA）、脱氧胆酸（DCA）和甘氨脱氧胆酸（GDCA）的血浆水平明显更高。在多元逻辑回归分析中，调整年龄和性别后，HA（优势比 [OR] 3.21，p < 0.001）、IPA（OR 2.59，p = 0.031）和 GDCA（OR 2.82，p = 0.036）的血浆水平与 PD 阳性状态相关。在调整混杂因素后，这些肠道代谢物的浓度与 MDS-UPDRS 第三部分评分或 MMSE 不相关。微生物代谢产物水平与促炎肠道细菌的相对丰度相关。
在 PD 患者中观察到与特定肠道微生物群变化相关的 HA、吲哚衍生物和次级胆汁酸等异常肠道微生物代谢物。
