Institute of Statistics, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
Department of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Front Cell Infect Microbiol. 2022 May 11;12:871710. doi: 10.3389/fcimb.2022.871710. eCollection 2022.
Parkinson's disease (PD) is a worldwide neurodegenerative disease with an increasing global burden, while constipation is an important risk factor for PD. The gastrointestinal tract had been proposed as the origin of PD in Braak's gut-brain axis hypothesis, and there is increasing evidence indicating that intestinal microbial alteration has a role in the pathogenesis of PD. In this study, we aim to investigate the role of intestinal microbial alteration in the mechanism of constipation-related PD.
We adapted our data from Hill-Burns et al., in which 324 participants were enrolled in the study. The 16S rRNA gene sequence data were processed, aligned, and categorized using DADA2. Mediation analysis was used to test and quantify the extent by which the intestinal microbial alteration explains the causal effect of constipation on PD incidence.
We found 18 bacterial genera and 7 species significantly different between groups of constipated and non-constipated subjects. Among these bacteria, nine genera and four species had a significant mediation effect between constipation and PD. All of them were short-chain fatty acid (SCFA)-producing bacteria that were substantially related to PD. Results from the mediation analysis showed that up to 76.56% of the effect of constipation on PD was mediated through intestinal microbial alteration.
Our findings support that gut dysbiosis plays a critical role in the pathogenesis of constipation-related PD, mostly through the decreasing of SCFA-producing bacteria, indicating that probiotics with SCFA-producing bacteria may be promising in the prevention and treatment of constipation-related PD.
帕金森病（PD）是一种全球性神经退行性疾病，全球负担日益加重，而便秘是 PD 的重要危险因素。在 Braak 的肠-脑轴假说中，胃肠道被认为是 PD 的起源，越来越多的证据表明，肠道微生物的改变在 PD 的发病机制中起作用。在这项研究中，我们旨在研究肠道微生物改变在便秘相关 PD 发病机制中的作用。
我们改编了 Hill-Burns 等人的数据，其中 324 名参与者被纳入研究。使用 DADA2 对 16S rRNA 基因序列数据进行处理、对齐和分类。中介分析用于测试和量化肠道微生物改变解释便秘对 PD 发病率的因果效应的程度。
我们发现 18 个细菌属和 7 个种在便秘和非便秘组之间存在显著差异。在这些细菌中，有 9 个属和 4 个种在便秘和 PD 之间具有显著的中介效应。所有这些细菌都是产生短链脂肪酸（SCFA）的细菌，与 PD 有实质性的关系。中介分析的结果表明，便秘对 PD 的影响有高达 76.56%是通过肠道微生物改变介导的。
我们的研究结果支持肠道菌群失调在便秘相关 PD 的发病机制中起着关键作用，主要是通过减少产生 SCFA 的细菌，这表明具有产生 SCFA 的细菌的益生菌可能在预防和治疗便秘相关 PD 方面具有广阔的前景。
1）原始数据集中没有提供一些应该调整的潜在混杂因素。2）我们的研究是基于便秘是 PD 的病因这一假设进行的；然而，便秘和 PD 可能相互影响。3）需要进一步的研究来解释便秘导致 PD 的剩余 23.44%的作用。
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