Microbiome, Pesticides and Parkinsons in Latinos

抽象的。这是对微生物组，农药和帕金森氏症（MEP; PI：Dr Ritz）研究的补充，目的是 招募更多的高度接触杀虫剂的拉丁裔社区成员。MEP研究假设a） 人类微生物组受到慢性环境暴露，特别是杀虫剂的影响;和B）改变的肠道 微生物组的组成或功能有助于帕金森病（PD）中神经变性的进展。PD 是一种进行性神经退行性疾病，具有重要的非运动功能，包括胃肠道（GI） 便秘和胃轻瘫等症状。人体微生物组在摄取和处理 营养素，药物和毒素;并影响免疫系统。微生物组影响神经系统的证据 功能，大脑活动和行为通过'肠-脑-轴'正在增长。环保部建议，农药也影响 微生物组和人类免疫系统在PD中的作用。肠道微生物组在PD中的作用尚未充分探索， 已经解决了毒素是否通过微生物组影响神经变性。MEP研究使用了一个地理 基于信息系统（GIS）模型的农药暴露模型，该模型基于加州州农药使用记录 报告（PUR）系统，该系统是在我们以前的帕金森病易感基因上开发的， 农药研究（PEG; R01 ES-010544）。沿着加州大学洛杉矶分校消化疾病分部，环境保护部提议， 分析400名PD患者和600名（200个年龄匹配的家庭和400个年龄性别匹配的社区）的肠道微生物组 对照使用16S核糖体RNA评估微生物群的相对丰度，目的是评估微生物群 农药暴露与非暴露对照和PD患者的组成和功能。在200例新发PD患者中， 在这100名药物初治（MN）PD患者中，我们收集了暴露、肠道动力指标和粪便样本的数据， 代谢组学和基于培养的实验（开始PD药物治疗前后）;评估相对 使用16S核糖体RNA和鸟枪宏基因组学和进行代谢组学 （血液或粪便）分析新发PD患者（两次，纵向）及其家庭对照。我们现在 建议有针对性地努力招募更多的拉丁裔参与者参加我们的研究，因为他们最容易受到 农药拉丁美洲人在加州中央谷的农业社区生活和工作， 在环境暴露和获得医疗保健方面的差距。在这些不同的国家建立信任是非常重要的， 社区能够加强拉丁美洲参与者的招聘。弗洛雷斯医生是拉丁裔社区的一员 并熟悉中央谷当地的医疗机构。她是唯一有资格解决这个问题的目标， 补充，以帮助增加拉丁美洲人在这一重要研究的参与。她将受益于 在加州大学洛杉矶分校的完善的研究环境工作，并将扩大她的专业知识，以解决 在流行病学研究的背景下，少数民族社区的环境问题，同时接受 该领域经验丰富的研究人员。这项研究有望为成长中的老年人提出新的预防选择 慢性环境暴露人群。

Abstract. This is a supplement to the Microbiome, Pesticides and Parkinson’s (MEP; PI: Dr Ritz) study with the goal to enroll a larger number of highly pesticide-exposed Latino community members. The MEP study hypothesized that a) the human microbiome is affected by chronic environmental exposures, specifically pesticides; and b) an altered gut microbiome composition or function contributes to the progression of neurodegeneration in Parkinson’s disease (PD). PD is a progressive neurodegenerative disease and has important non-motor features including gastro-intestinal (GI) symptoms such as constipation and gastroparesis. The human microbiome has a major role in the uptake and handling of nutrients, medications, and toxins; and affects the immune system. Evidence that the microbiome affects neurologic function, brain activity, and behavior via the ‘gut-brain-axis’ is growing. MEP proposed that pesticides also influence the microbiome and the human immune system in PD. The role of the gut microbiome in PD is underexplored and no study has addressed whether toxins influence neurodegeneration via the microbiome. The MEP study uses a geographic information system (GIS) model-based pesticide exposure model based on records from the California state pesticide use reporting (PUR) system that has been developed in on our previous Parkinson's Disease Susceptibility Genes and Pesticides Study (PEG; R01 ES-010544). Along with the UCLA Division of Digestive Diseases, MEP proposed to analyze the gut microbiome of 400 PD patients and 600 (200 age-matched household & 400 age-sex matched community) controls using 16S ribosomal RNA to assess relative abundance of microbiota with the goal to assess microbiome composition and function in pesticide exposed vs. non-exposed controls and PD patients. In 200 new-onset PD patients, of these 100 medication naïve (MN) PD patients, we collect data on exposures, gut motility indicators, and fecal samples for metabolomics and culture based experiments (before and after starting PD medications); assess differences in relative abundances of microbes over time using 16S ribosomal RNA and shotgun metagenomics and conduct metabolomics (blood or stool) analyses for new onset PD patients (twice, longitudinally) and their household controls. We are now proposing to make a targeted effort to enroll more Latino participants in our study as they are the most highly exposed to pesticides. Latinos live and work in the farming communities of California’s Central Valley and experience unjust disparities in environmental exposures and health care access. It is very important to build trust in these diverse communities to be able to enhance recruitment of Latino participants. Dr. Flores is a member of the Latino community and is familiar with the local health care settings in the central valley. She is uniquely qualified to address the goals of this supplement in order to help increase the participation of Latinos in this important study. She will greatly benefit from working in the well-established research environment of UCLA and will be expanding her expertise to address environmental issues in minority communities in the context of an epidemiologic study while being mentored by experienced researchers in the field. This research is expected to suggest novel prevention options for a growing elderly population with chronic environmental exposures.