Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
Mov Disord. 2024 Oct;39(10):1740-1751. doi: 10.1002/mds.29959. Epub 2024 Aug 28.
Parkinson's disease (PD) has been consistently linked to alterations within the gut microbiome.
Our goal was to identify microbial features associated with PD incidence and progression.
Metagenomic sequencing was used to characterize taxonomic and functional changes to the PD microbiome and to explore their relation to bacterial metabolites and disease progression. Motor and non-motor symptoms were tracked using Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and levodopa equivalent dose across ≤5 yearly study visits. Stool samples were collected at baseline for metagenomic sequencing (176 PD, 100 controls).
PD-derived stool samples had reduced intermicrobial connectivity and seven differentially abundant species compared to controls. A suite of bacterial functions differed between PD and controls, including depletion of carbohydrate degradation pathways and enrichment of ribosomal genes. Faecalibacterium prausnitzii-specific reads contributed significantly to more than half of all differentially abundant functional terms. A subset of disease-associated functional terms correlated with faster progression of MDS-UPDRS part IV and separated those with slow and fast progression with moderate accuracy within a random forest model (area under curve = 0.70). Most PD-associated microbial trends were stronger in those with symmetric motor symptoms.
We provide further evidence that the PD microbiome is characterized by reduced intermicrobial communication and a shift to proteolytic metabolism in lieu of short-chain fatty acid production, and suggest that these microbial alterations may be relevant to disease progression. We also describe how our results support the existence of gut-first versus brain-first PD subtypes. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
帕金森病（PD）与肠道微生物组的改变一直存在关联。
我们的目标是确定与 PD 发病和进展相关的微生物特征。
使用宏基因组测序来描述 PD 微生物组的分类和功能变化，并探索其与细菌代谢物和疾病进展的关系。使用运动障碍协会统一帕金森病评定量表（MDS-UPDRS）和左旋多巴等效剂量在≤5 年的研究访视中跟踪运动和非运动症状。在基线时收集粪便样本进行宏基因组测序（176 例 PD，100 例对照）。
与对照组相比，PD 来源的粪便样本中微生物间的连通性降低，且有 7 种差异丰度物种。PD 和对照组之间存在一系列细菌功能差异，包括碳水化合物降解途径的耗竭和核糖体基因的富集。普拉梭菌（Faecalibacterium prausnitzii）的特异性读段对超过一半的差异丰度功能术语有显著贡献。与 MDS-UPDRS 第四部分进展更快相关的疾病相关功能术语子集在随机森林模型中具有中等准确性（曲线下面积为 0.70）。在具有对称运动症状的患者中，与疾病相关的大多数微生物趋势更为明显。
我们提供了进一步的证据，表明 PD 微生物组的特征是微生物间通讯减少，以及向蛋白水解代谢转变，而不是短链脂肪酸的产生，并表明这些微生物变化可能与疾病进展有关。我们还描述了我们的结果如何支持存在“肠道优先于大脑”的 PD 亚型。© 2024 作者。运动障碍协会由 Wiley 期刊出版公司代表国际帕金森和运动障碍协会出版。
