Metabolic, Microbiome and Toxicant-Related Interactions (MATRIX)

代谢、微生物组和毒物相关的相互作用 (MATRIX)

基本信息

批准号：
9145194
负责人：
Dean Paul Jones
金额：
$ 16.23万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9145194
关键词：
37 weeks gestation Accounting Address Affect African American Anti-Inflammatory Agents Anti-inflammatory Antibiotics Area Bioinformatics Biological Markers Birth Caucasians Child Child health care Chronic Chronic stress Clinical Treatment Complex Corwin Data Development Diet Disease Dose Endogenous Factors Enrollment Environment Environmental Exposure Estrogen Metabolism Ethnic Origin Etiology Exogenous Factors Exposure to Extracellular Matrix Degradation Failure Family Funding Gestational Age Health Health Personnel Human Immune Incidence Individual Infant Infection Inflammation Inflammatory Invaded Knowledge Link Longitudinal Studies Measurement Metabolic Metabolic Pathway Metabolism Methods Molecular Mothers Newborn Infant Outcome Parents Pathway interactions Phenotype Plasma Population Predisposition Pregnant Women Premature Birth Preventive therapy Race Research Research Support Resolution Resources Risk Risk Behaviors Risk Factors Sampling Science Serum Socioeconomic Status Stress TNFRSF5 gene Testing Time Tissues Toxic Environmental Substances Toxicant exposure Treatment outcome United States United States National Institutes of Health Universities Vagina Vitamin D Woman adverse outcome biological adaptation to stress cohort cytokine early life exposure experience fetal gut microbiome high risk knowledge base maternal stress member metabolome metabolomics microbial community microbiome neurodevelopment oral microbiome postnatal pregnant prenatal prenatal stress prevent racial disparity ranpirnase socioeconomics toxicant vaginal microbiome

项目摘要

ABSTRACT – Project 3 Most complex health conditions do not have a single etiology, but rather develop from exposure to multiple exogenous and endogenous factors that interact to influence individual susceptibility. Failure to consider these multiple and complex interactions reduces the ability of health care providers to accurately predict the occurrence of disease and appropriately target preventive therapies. In Project 3, we propose to leverage the combined expertise of the members of this P50 application with the resources of two pillar studies – our recently initiated 5-year study (R01 NR014800) assessing the maternal prenatal microbiome as predictive of birth outcomes in a large and socioeconomically diverse cohort of pregnant African American (AA) women; and the analytic and bioinformatic resources of Emory University’s NIH-funded Human Exposome Research Center (HERCULES; P30 ES019776) – in order to characterize the complex interactions of pre- and postnatal environmental toxicant exposures, microbiome composition, and associated metabolic pathways that underlie the development of two serious child health conditions, preterm birth and neurodevelopmental delay. Preterm birth and neurodevelopmental delay carry lifelong consequences for children and their families. Neither the occurrence of preterm birth nor neurodevelopmental delay is equally distributed within the US population. The incidence of preterm birth in Caucasian infants is 1:10, whereas it is 1:6 for AA infants, resulting in more than 30,000 AA infants born preterm each year in the United States. Neurodevelopmental delay is likewise more common in AA children, and racial disparities in neurodevelopmental delay persist or worsen across development, even when accounting for socioeconomic status and rates of preterm birth. Also more common among AA families are exposures to environmental toxicants, maternal prenatal infections and inflammation, and chronic stress – all independent risk factors for preterm birth and neurodevelopmental delay. Most recently, race-related differences in the vaginal microbiome have been identified as well, with AA women harboring vaginal microbial communities associated with higher risk of infection. Research to uncover the interactions between these factors and to identify the underpinning molecular pathways has barely begun. In Project 3 we will advance the science in this area by characterizing the following for 300 AA mother- infant pairs derived from the Parent Study: (1) the metabolites and metabolic pathways that associate with preterm birth and neurodevelopmental delay, and (2) the metabolites and pathways that correlate with the maternal prenatal microbiome (data from the Parent Study), maternal prenatal and infant postnatal environmental toxicant exposures (data from Project 1), and the infant microbiome and neurodevelopmental delay (data from Project 2). By unraveling these complex relationships, Project 3 will contribute to the ability to predict these adverse outcomes and appropriately target preventive therapies.

摘要 - 项目3 大多数复杂的健康状况没有单一的病因，而是从接触到相互作用以影响个体敏感性的多个外源和内源性因素。无法考虑这些多重和复杂的相互作用可降低医疗保健提供者准确的能力预测疾病的发生并适当靶向预防疗法。在项目3中，我们建议利用该P50应用程序成员的总专业知识以及两个支柱研究的资源 - 我们最近启动的5年研究（R01 NR014800）评估母体产前微生物组预测大型且社会经济多样化的非裔美国人（AA）中的出生结果女性;以及埃默里大学（Emory University）NIH资助的人类展览组的分析和生物信息学资源研究中心（Hercules; P30 ES019776） - 为了表征前和之前的复杂相互作用产后环境有毒物质暴露，微生物组组成和相关的代谢途径是两个严重的儿童健康状况，早产和神经发育延迟的发展。早产和神经发育延迟会给儿童及其家人带来终身后果。在美国，早产出生和神经发育延迟的发生均未分布人口。高加索婴儿的早产事件是1:10，而AA婴儿的1：6，在美国，每年有30,000多名AA婴儿出生的婴儿。神经发育同样，延迟在AA儿童中更为常见，而神经发育延迟中的种族分布持续存在或即使考虑到社会经济状况和早产率，在整个发展中都会恶化。还 AA家庭中更常见的是对环境有毒物质，母体产前感染和炎症和慢性压力 - 早产和神经发育延迟的所有独立危险因素。最近，也发现了与种族相关的阴道微生物组的差异，AA女性具有与较高感染风险相关的阴道微生物群落。研究以发现这些因素之间的相互作用并确定基础分子途径几乎没有开始。在项目3中，我们将通过描述以下300 aa母亲来推进该领域的科学。来自父母研究的婴儿对：（1）与早产和神经发育延迟，以及（2）与母亲产前微生物组（来自父母研究的数据），产前和婴儿产后环境有毒物质暴露（项目1的数据）以及婴儿微生物组和神经发育延迟（项目2的数据）。通过揭示这些复杂的关系，项目3将有助于预测这些不良结果并适当靶向预防疗法。