Functional interaction between the gut microbiome and arsenic exposure

肠道微生物组与砷暴露之间的功能相互作用

基本信息

批准号：
9187023
负责人：
Kun Lu
金额：
$ 42.37万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-02-05 至 2019-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9187023
关键词：
Address Affect Animal Model Animals Applications Grants Arsenic Bacteria Bile Acids Carcinogens Cardiovascular Diseases Communities Data Disease Dose Environmental Exposure Environmental Pollutants Exposure to Fingerprint Foundations Future Goals Health Homeostasis Human Human Microbiome Immune response Impairment Individual Intake Intestines Laboratories Link Malignant Neoplasms Mediating Metabolic Metabolic Biotransformation Metabolic Diseases Metabolism Molecular Oral Oxidative Stress Permeability Phenotype Predisposition Principal Investigator Production Public Health Research Research Personnel Risk Factors Role Route Structure System Taxonomy Technology Testing Time Tissues Toxic effect Toxicology Water base computerized tools design expectation gut microbiome gut microbiota human disease immune function innovation metabolomics microbiome novel public health relevance quorum sensing response skin lesion stem

项目摘要

DESCRIPTION (provided by Principal Investigator): There is a fundamental gap in understanding the role of environmental exposure-gut microbiome interactions in affecting human health. The microbiome of the human intestinal tract has a profound effect on human health through its key role in a wide range of host-related functions. Exposure to inorganic arsenic (iAs) is a significant public health issue worldwide and has been linked to a number of diseases, including cancers, metabolic disorders, cardiovascular diseases and impaired immune functions. Mounting evidence indicates that dysregulated gut microflora contribute significantly to many of these diseases, underscoring a potentially important role of the gut microbiome in arsenic-induced diseases. However, functional interaction between the gut microbiome and arsenic exposure is largely unexplored, except for the investigators' recent studies. Their central hypothesis is that the gut microbiome-arsenic interaction influences iAs toxicity. This hypothesis has been formulated on the basis of exciting preliminary data produced in the Principal Investigator's laboratory and will be tested by pursuing three specific aims, with the goal of defining the effects of iAs on the gut microbiome and its function and elucidating the role of gut microbiome community structures in mediating arsenic toxicity. The significance of this grant application lies in the fact that gut microbiome-exposure interaction is still largely unexplored despite the diverse and profound roles of the microbiome in human health. The investigators' proposed studies are also highly innovative and represent a paradigm shift in toxicology because they focus on gut microbiome perturbations as a novel mechanism of exposure-induced diseases and an unexplored risk factor responsible for individual susceptibility. The innovation of this grant application also stems from the novel application of integrated bioanalytical and computational tools to a systems-level study of a significant gut microbiome-exposure interaction. Findings from this study are expected to lay a foundation for future studies aiming at expanding our understanding of new mechanisms by which exposure to iAs leads to or exacerbates human disease: the role of the microbiome.

描述（由首席研究员提供）：在了解环境暴露与肠道微生物组相互作用对人类健康的影响方面存在根本性差距人类肠道微生物组通过其在广泛领域中的关键作用对人类健康产生深远影响。越来越多的证据表明，接触无机砷 (iAs) 是一个重大的公共卫生问题，与许多疾病有关，包括癌症、代谢紊乱、心血管疾病和免疫功能受损。表明肠道菌群失调导致了许多此类疾病，强调了肠道微生物组在砷诱发的疾病中潜在的重要作用。然而，除了研究人员最近的研究外，肠道微生物组与砷暴露之间的功能相互作用在很大程度上尚未被探索。他们的中心假设是肠道微生物组与砷的相互作用影响砷的毒性。该假设是根据首席研究员实验室产生的令人兴奋的初步数据制定的，并将通过追求三种特定的方法进行测试。目标，与确定 iAs 对肠道微生物组及其功能的影响，并阐明肠道微生物组群落结构在介导砷毒性中的作用，这项资助申请的意义在于，尽管肠道微生物组与暴露的相互作用在很大程度上仍未得到探索。研究人员提出的研究也具有高度创新性，代表了毒理学的范式转变，因为他们将肠道微生物扰动作为一种新机制。该拨款申请的创新还源于将集成生物分析和计算工具应用于重要肠道微生物组与暴露相互作用的系统级研究。研究预计将为未来的研究奠定基础，旨在扩大我们对接触异砷导致或恶化人类疾病的新机制的理解：微生物组的作用。