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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.