Early life metal exposure, the gut microbiome, and neurodevelopment in childhood

生命早期的金属暴露、肠道微生物组和儿童期的神经发育

• 批准号: 10883857
• 负责人: Shoshannah Iylene Eggers
• 金额: $ 24.89万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-26 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10883857
• 关键词: 11 year old; Address; Adolescence; Age; Area; Attention; Behavioral; Biological; Biological Markers; Biology; Biometry; Birth; Blood; Brain; Chemical Exposure; Chemicals; Childhood; Cities; Clinical; Collaborations; Copper; Cross-Sectional Studies; Data; Data Analyses; Development; Environment; Environmental Epidemiology; Environmental Exposure; Environmental Health; Epidemiologist; Faculty; Faith; Feces; Foundations; Funding; Future; Goals; Growth; Hair; Health; Human; Human Microbiome; Hydrocortisone; Individual; Infant; Intervention; Knowledge; Laboratories; Lead; Learning; Life; Link; Manganese; Measurement; Measures; Mediation; Mentors; Mentorship; Metabolic; Metagenomics; Metal exposure; Metals; Methodology; Mexico; Microbiology; Modeling; National Institute of Environmental Health Sciences; Neurologic; Neurological outcome; Obesity; Observational Study; Pathway interactions; Play; Positioning Attribute; Predisposition; Proteobacteria; Protocols documentation; Research; Research Activity; Research Personnel; Research Proposals; Resolution; Role; Rotation; Second Pregnancy Trimester; Secure; Shapes; Shotguns; Time; Tooth structure; Training; Training Activity; Work; Zinc; behavior measurement; career; career development; cohort; early detection biomarkers; early life exposure; epidemiology study; executive function; fetal; gut bacteria; gut microbiome; gut-brain axis; infancy; innovation; interest; meetings; metabolome; metabolomics; metagenomic sequencing; microbial; microbiome; microbiome analysis; microbiome composition; microbiome research; multidimensional data; multidisciplinary; multiple omics; neurobehavioral; neurodevelopment; neurotoxicology; novel; pilot test; prenatal; prenatal exposure; prospective; research and development; sample collection; skill acquisition; skills; social stressor; stool sample; success; symposium; tenure track; time use

PROJECT SUMMARY I am an environmental epidemiologist and microbiome researcher with a primary research interest in the role of the human microbiome between environmental exposures and human health, including neurological outcomes. The goal of this proposal is to obtain training and acquire the skills needed to continue to build my academic research career by linking early life metal exposure, the gut microbiome and metabolome in childhood, and neurodevelopmental measures of attention. For this proposal, I plan to train with an expert team of mentors, collaborators, and advisors with transdisciplinary expertise in exposomics, exposure biology, neurodevelopment, biostatistics, metabolomics, epidemiology, and microbiome research. The proposed training plan includes clinical and laboratory rotations, coursework, seminars and meetings, conferences, and 1-on-1 tutorials with mentors and advisors, covering research and career development topics. This training will provide skills and knowledge in the areas of neurodevelopment, and exposomics, including exposure biology and multi-omics analysis. Upon completion of this training plan, I will be able to achieve my long-term career goal of becoming an independent researcher focused on the inter-relationships among environmental exposures, the microbiome, and neurodevelopment. To that end, I propose leveraging the use of the established Programming Research in Obesity, GRowth, Environment and Social Stressors (PROGRESS) birth cohort, based in Mexico City, and adding microbiome analysis. Specifically, I will: 1) train with Dr. Arora in exposure biology and analysis of baby teeth as a biomarker of early life metal exposure; 2) train with Dr. Wright, in collaboration with Dr. Shamesh, in neurodevelopmental assessment, principals of neurotoxicology, and their use in epidemiologic studies; 3) train with Dr. Faith in metagenomic analysis, 4) integrate biostatistical assessment of mixtures and high dimensional data, guided by Dr. Gennings; 4) learn about stool metabolomic analysis methodology with Dr. Walker; 5) work with Dr. Tellez-Rojo to facilitate stool sample collection and data analysis in PROGRESS. I will use these training and research activities to integrate the microbiome into an exposomic analysis of neurodevelopment. I will use the research and career development training I receive to establish myself as an independent investigator with a tenure track faculty position, able to secure R01 funding. This research proposal combines innovative measures of exposure, novel data analysis approaches, and high resolution omics analysis to address gaps in the understanding of timing and potential mechanisms by which metal exposures, and the gut microbiome and metabolome, are associated with neurodevelopmental measures of attention. The proposed research and training plan builds the foundation for an independent research career that aims to clarify the links between environmental exposures and neurodevelopment, via the human microbiome.

项目摘要 我是一名环境流行病学家和微生物组研究人员，对作用的主要研究兴趣 环境暴露与人类健康之间的人类微生物组，包括神经学结果。 该建议的目的是获得培训并获得继续建立我的学术所需的技能 通过将早期生命金属暴露，童年时代的肠道微生物组和代谢组联系起来，研究职业 神经发育的关注度量。 对于此建议，我计划与一支由导师，合作者和顾问团队一起培训 跨学科的专业知识，暴露生物学，神经发育，生物统计学，代谢组学，，代谢组学专业知识 流行病学和微生物组研究。拟议的培训计划包括临床和实验室旋转， 课程，研讨会和会议，会议以及与导师和顾问的一对一教程，涵盖 研究和职业发展主题。该培训将在该领域提供技能和知识 神经发育和外汇学，包括暴露生物学和多词分析。完成后 这个培训计划，我将能够实现成为独立研究人员的长期职业目标 专注于环境暴露，微生物组和神经发育之间的关系。 为此，我建议利用在肥胖，增长， 环境和社会压力源（进度）出生队列，位于墨西哥城，并增加微生物组 分析。具体来说，我将：1）与Arora博士一起在暴露生物学中训练，并将乳牙分析为 早期金属暴露的生物标志物； 2）与赖特博士一起训练，与Shamesh博士合作 神经发育评估，神经毒理学的原理及其在流行病学研究中的使用； 3）火车 通过宏基因组分析的信仰博士，4）整合混合物的生物统计评估和高维度 数据，由Gennings博士指导； 4）与Walker博士了解粪便代谢组分析方法； 5）工作 借助Tellez-Rojo博士，可以促进正在进行的粪便样本收集和数据分析。我会用这些 培训和研究活动，将微生物组整合到神经发育的外汇分析中。我 将利用我接受的研究和职业发展培训来确立自己为独立的 具有任期教师职位的调查员能够获得R01资金。 该研究建议结合了暴露的创新度量，新型数据分析方法， 以及高分辨率的OMICS分析，以解决理解时间和潜在机制的差距 金属暴露以及肠道微生物组和代谢组与神经发育有关 注意力衡量。拟议的研究和培训计划为独立的基础奠定了基础 旨在阐明环境暴露与神经发育之间的联系的研究职业 人类微生物组。