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

• 批准号: 8814331
• 负责人: Kun Lu
• 金额: $ 60.84万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 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/8814331
• 关键词: Address; Affect; Animal Model; Animals; Applications Grants; Arsenic; Bacteria; Bile Acids; Carcinogens; Cardiovascular Diseases; Coenzymes; Communities; Data; Disease; Dose; Environmental Exposure; Environmental Pollutants; Exposure to; Figs - dietary; Fingerprint; Foundations; Future; Genomics; Goals; Health; Homeostasis; Human; Human Microbiome; Immune response; 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; Stress; Structure; System; Technology; Testing; Time; Tissues; Toxic effect; Toxicology; base; computerized tools; design; drinking water; expectation; gut microflora; human disease; immune function; innovation; metabolomics; microbiome; novel; public health relevance; quorum sensing; response; skin lesion; stem

 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（由首席研究者提供）：了解环境暴露量微生物组相互作用在影响人类健康中的作用存在根本差距。人类肠道的微生物组通过其在广泛的宿主相关功能中的关键作用对人类健康产生了深远的影响。接触无机砷（IAS）是全球重大的公共卫生问题，与多种疾病有关，包括癌症，代谢疾病，心血管疾病和免疫功能受损。越来越多的证据表明，肠道菌群失调对许多疾病有显着贡献，强调了肠道微生物组在砷诱导的疾病中的潜在重要作用。然而，除了研究人员最近的研究外，肠道微生物组和砷暴露之间的功能相互作用在很大程度上是出乎意料的。它们的中心假设是肠道微生物组砷的相互作用会影响IAS毒性。该假设是根据首席研究者实验室中产生的令人兴奋的初步数据提出的，并将通过追求三个特定目标来检验 定义IAS对肠道微生物组及其功能的影响的目的，并阐明了肠道微生物组社区结构在介导砷毒性中的作用。该赠款应用的重要性在于这样一个事实，即肠道微生物组的相互作用仍然出乎意料地出乎意料地意外地希望微生物组在人类健康中的潜水员和深刻的作用。研究者的拟议研究也具有很高的创新性，代表了毒理学的范式转变，因为它们专注于肠道微生物组扰动，这是暴露诱发的疾病的新机制，并且是导致个人易感性的意外风险因素。该赠款应用的创新也从集成的生物分析和计算工具的新应用到对重要肠道微生物组相互作用的系统级研究。预计这项研究的结果将为未来的研究奠定基础，旨在扩大我们对新机制的理解，通过这种机制导致IAS导致或加剧人类疾病的新机制：微生物组的作用。