The Gut Microbiome in Parkinson Disease

项目摘要/摘要 这是第一次R01申请的早期阶段，新的研究人员和目前的NIEHS K01奖获得者。 帕金森病(PD)是一种无法治愈的致残性神经退行性疾病。早在几年前 帕金森病的诊断和运动症状的出现，帕金森病患者会出现非运动症状，包括， 重要的是，便秘和胃肠功能障碍。便秘影响80%以上的帕金森病患者 帕金森病的最强危险因素之一。最近的研究表明，肠道和肠道中的神经系统 迷走神经的背侧运动核在解剖学上连接胃肠道系统和大脑，是 第一个也是最严重的受α-突触核蛋白病理特征影响的PD5导致 假设胃肠道可能是帕金森病的起始部位。 我们建议对人类肠道微生物群与帕金森病的关系进行全面的研究。 重点关注起病前的微生物群。我们将通过建立一个正在进行的国防部来实现这一点 资助的项目，已确定参与者患有帕金森前期综合症(PPS-定义为共同 便秘、pRBD(可能的快速眼动睡眠行为障碍)和营养不良的发生 在一项初步研究中，帕金森病的风险增加了约200倍。研究其中的微生物群 他们极有可能发展为帕金森病或已经处于运动前状态，他们将给我们提供一个独特的视角 在饮食和生活方式改变对帕金森病患者产生任何潜在的疾病相关影响之前 可能混淆了先前的病例对照研究。这项拟议的研究将利用25年的 前瞻性收集关于环境和饮食暴露以及两种预期疾病结局的数据 一群男人和女人。

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.