Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
Michael Smith Laboratories, UBC, Vancouver, British Columbia, Canada.
Mov Disord. 2020 Jul;35(7):1208-1217. doi: 10.1002/mds.28052. Epub 2020 May 1.
Parkinson's disease is characterized by a high burden of gastrointestinal comorbidities, especially constipation and reduced colonic transit time, and by gut microbiota alterations. The diverse metabolites produced by the microbiota are broadly relevant to host health. How microbiota composition and metabolism relate to gastrointestinal function in Parkinson's disease is largely unknown. The objectives of the current study were to assesses associations between microbiota composition, stool consistency, constipation, and systemic microbial metabolites in Parkinson's disease to better understand how intestinal microbes contribute to gastrointestinal disturbances commonly observed in patients.
Three hundred participants (197 Parkinson's patients and 103 controls) were recruited for this cross-sectional cohort study. Participants supplied fecal samples for microbiota sequencing (n = 300) and serum for untargeted metabolomics (n = 125). Data were collected on motor and nonmotor Parkinson's symptoms, medications, diet, and demographics.
Significant microbiota taxonomic differences were observed in Parkinson's patients, even when controlling for gastrointestinal function. Parkinson's microbiota was characterized by reduced carbohydrate fermentation and butyrate synthesis capacity and increased proteolytic fermentation and production of deleterious amino acid metabolites, including p-cresol and phenylacetylglutamine. Taxonomic shifts and elevated proteolytic metabolites were strongly associated with stool consistency (a proxy for colonic transit time) and constipation among patients.
Compositional and metabolic alterations in the Parkinson's microbiota are highly associated with gut function, suggesting plausible mechanistic links between altered bacterial metabolism and reduced gut health in this disease. The systemic detection of elevated deleterious proteolytic microbial metabolites in Parkinson's serum suggests a mechanism whereby microbiota dysbiosis contributes to disease etiology and pathophysiology. © 2020 International Parkinson and Movement Disorder Society.
帕金森病的胃肠道合并症负担很高，尤其是便秘和结肠传输时间缩短，以及肠道微生物群的改变。微生物群产生的多种代谢物与宿主健康广泛相关。肠道微生物群的组成和代谢与帕金森病的胃肠道功能之间的关系在很大程度上尚不清楚。本研究的目的是评估肠道微生物群组成、粪便稠度、便秘和系统性微生物代谢物之间的关联，以更好地了解肠道微生物如何导致帕金森病患者中常见的胃肠道紊乱。
本横断面队列研究招募了 300 名参与者（197 名帕金森病患者和 103 名对照者）。参与者提供了粪便样本进行微生物组测序（n=300）和血清进行非靶向代谢组学分析（n=125）。收集了参与者的运动和非运动性帕金森病症状、药物、饮食和人口统计学数据。
即使在控制胃肠道功能的情况下，帕金森病患者的肠道微生物群也存在显著的分类学差异。帕金森病微生物群的特征是碳水化合物发酵和丁酸盐合成能力降低，而蛋白水解发酵和有害氨基酸代谢物（包括对甲酚和苯乙酰谷氨酰胺）的产生增加。分类学变化和升高的蛋白水解代谢物与患者的粪便稠度（结肠传输时间的替代指标）和便秘密切相关。
帕金森病微生物群的组成和代谢改变与肠道功能高度相关，这表明在这种疾病中，细菌代谢改变与肠道健康状况不佳之间存在合理的机制联系。帕金森病血清中检测到升高的有害蛋白水解微生物代谢物表明，微生物失调通过何种机制促进了疾病的病因和发病机制。© 2020 国际帕金森病和运动障碍学会。
