Microbiome, Pesticides and Parkinsons in Latinos

拉丁美洲人的微生物组、农药和帕金森病

• 批准号: 10415745
• 负责人: Beate R Ritz
• 金额: $ 14.82万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10415745
• 关键词: Address; Affect; Age; Agriculture; Animals; Area; Behavior; Biological; Biological Models; Blood; Brain; California; Caring; Chronic; Clinical; Clinical Trials; Communities; Constipation; County; Data; Diagnosis; Digestive System Disorders; Disease; Disease Progression; Doctor of Philosophy; Early Diagnosis; Elderly; Enrollment; Ensure; Environment; Environmental Exposure; Environmental Health; Etiology; Exposure to; Farming Community; Farming environment; Feces; Functional disorder; Funding; Gastroparesis; Geographic Information Systems; Goals; Grant; Health Personnel; Hispanics; Household; Human; Human Microbiome; Immigrant; Immune system; Intervention; Language; Latino; Measures; Mentors; Metabolic Pathway; Metagenomics; Microbe; Minority Groups; Modeling; National Institute of Environmental Health Sciences; Nerve Degeneration; Nervous System Physiology; Neurodegenerative Disorders; Neurologist; Nutrient; Onset of illness; Parkinson Disease; Participant; Pathway interactions; Patients; Pesticides; Pharmaceutical Preparations; Physicians; Population; Population Heterogeneity; Population Research; Prevention; Process; Public Policy; RNA, Ribosomal, 16S; Records; Regulation; Reporting; Research; Research Personnel; Resources; Role; Rural; Sampling; Services; Shotguns; Subgroup; Susceptibility Gene; System; Toxin; Trust; Woman; Work; agricultural pesticide; base; cell motility; cohort; epidemiology study; experience; experimental study; farm worker; gastrointestinal symptom; gut microbiome; gut microbiota; gut-brain axis; health care availability; health care settings; improved; insight; intestinal epithelium; medical specialties; member; metabolomics; microbial; microbiome; microbiome composition; microbiota; minority communities; neglect; novel; novel therapeutics; pesticide exposure; prevent; recruit; residence; rural environment; rural health network; sex; social; time use; uptake

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.

抽象的。这是微生物组、杀虫剂和帕金森病(MEP；PI：Dr Ritz)研究的补充，目的是 招募更多高度接触杀虫剂的拉丁裔社区成员。环保部的研究假设a) 人体微生物群受到长期环境暴露的影响，特别是杀虫剂；和b)肠道改变 微生物组的组成或功能有助于帕金森病(PD)神经退行性变的进展。PD 是一种进行性神经退行性疾病，具有重要的非运动特征，包括胃肠道(GI)。 便秘和胃瘫等症状。人类微生物群在摄取和处理 营养素、药物和毒素；并影响免疫系统。微生物群影响神经学的证据 通过“肠-脑-轴”的功能、大脑活动和行为都在增长。环保部提出，杀虫剂也会影响 微生物群与帕金森病患者免疫系统的关系。肠道微生物群在帕金森病中的作用尚未得到充分研究，也没有研究 已经解决了毒素是否通过微生物群影响神经退化。环保部的研究使用了一个地理位置 基于加州农药使用记录的基于信息系统(GIS)模型的农药暴露模型 报告(PUR)系统，已经开发了关于我们以前的帕金森氏病易感基因和 农药研究(聚乙二醇；R01 ES-010544)。与加州大学洛杉矶分校的消化疾病部门一起，MEP建议 400例PD患者和600例PD患者肠道菌群分析(200户年龄匹配家庭和400个年龄性别匹配社区) 对照使用16S核糖体RNA评估微生物区系的相对丰度，目的是评估微生物组 接触农药者与非接触者和帕金森病患者的组成和功能。在200名新发的帕金森病患者中， 这100名药物幼稚(MN)PD患者，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)；评估相对差异 利用16S核糖体RNA和鸟枪式元基因组学研究微生物随时间的丰度并进行代谢组学研究 对新发的帕金森病患者(纵向两次)和他们的家庭对照进行(血液或粪便)分析。我们现在是 建议有针对性地努力在我们的研究中招募更多的拉丁裔参与者，因为他们是接触最多的 杀虫剂。拉美裔在加州中央山谷的农业社区生活和工作，经历着不公平的待遇 在环境暴露和卫生保健服务获得方面的差距。在这些不同的领域建立信任是非常重要的 社区能够加强对拉丁裔参与者的招募。弗洛雷斯博士是拉美裔社区的一员 并熟悉中央山谷的当地医疗保健环境。她是唯一有资格实现这一目标的人 补充资料，以帮助增加拉美裔人对这项重要研究的参与。她将极大地受益于 在加州大学洛杉矶分校完善的研究环境中工作，并将扩展她的专业知识以解决 在流行病学研究的背景下少数族裔社区的环境问题，同时由 该领域经验丰富的研究人员。这项研究有望为不断增长的老年人提供新的预防方案 长期暴露在环境中的人群。