The Gut Microbiome in Parkinson Disease

帕金森病中的肠道微生物组

• 批准号: 9403424
• 负责人: Natalia Palacios
• 金额: $ 47万
• 依托单位: UNIVERSITY OF MASSACHUSETTS LOWELL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-17 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9403424
• 关键词: Gut; Microbiome; Parkinson; Disease

Project Summary/Abstract This is a first R01 application from an early stage, new investigator and current NIEHS K01 awardee. Parkinson disease (PD) is a disabling neurodegenerative disease for which there is no cure. Years before the diagnosis of PD and the onset of motor symptoms, PD patients develop non-motor symptoms, including, importantly, constipation and gastrointestinal dysfunction. Constipation affects over 80% of PD patients and is one of the strongest risk factors for PD. Recent research shows that the enteric nervous system in the gut and the dorsal motor nucleus of the vagus nerve which anatomically links the GI system to the brain, are among the first and most severely affected by alpha-synuclein pathology characteristic of PD5 leading to the hypothesis that the gastrointestinal tract might be the site of initiation of PD. We propose to conduct a comprehensive investigation of the relation between human gut microbiome and PD, focusing on the pre- onset microbiome. We will do this by building on an ongoing Department of Defense funded project that has identified participants with pre-parkinson syndrome (PPS - defined as the co- occurrence of constipation, pRBD (probable rapid eye movement sleep behavior disorder) and hyposmia) that in a pilot study has been associated with a ~200 fold increase in PD risk. Studying the microbiome among this group, who are highly likely to develop PD or are already in the premotor state, will give us a unique look at the microbiome in PD patients prior to any potential disease-associated effects of changes in diet and lifestyle that may have confounded prior case-control studies. The proposed study will take advantage of 25 years of prospectively collected data on environmental and dietary exposures and disease outcomes in two prospective cohorts of men and women.

项目摘要/摘要 这是早期，新调查员和现任NIEHS K01获奖者的第一个R01应用程序。 帕金森氏病（PD）是一种无法治愈的神经退行性疾病。几年前 PD诊断和运动症状的发作，PD患者出现非运动症状，包括 重要的是，便秘和胃肠道功能障碍。便秘影响超过80％的PD患者，IS PD的最强风险因素之一。最近的研究表明，肠道中的肠神经系统和 迷走神经的背运动核从解剖学上将胃肠系统与大脑联系起来 PD5的第一个也是最严重受到α-突触核蛋白病理特征的影响，导致 假设胃肠道可能是PD启动的位置。 我们建议对人肠道微生物组和PD之间的关系进行全面研究， 专注于发作前的微生物组。我们将通过在持续的国防部建设来做到这一点 资助的项目已经确定参与者患有帕金森综合征（PPS-定义为共同） 便秘，PRBD（可能的快速眼动睡眠行为障碍）和低质量的发生） 在一项试点研究中，PD风险增加了约200倍。研究微生物组 非常有可能发展PD或已经处于前一场状态的小组将为我们提供独特的了解 PD患者的微生物组在饮食和生活方式变化的任何潜在疾病相关影响之前 可能已经混淆了先前的病例对照研究。拟议的研究将利用25年 前瞻性收集了有关两个前瞻性的环境和饮食暴露和疾病结果的数据 男女同伙。