Impact of Pathogenic and Protective Environmental Exposures on Autoimmune Disease

致病性和保护性环境暴露对自身免疫性疾病的影响

基本信息

批准号：
8970378
负责人：
DIANE L KAMEN
金额：
$ 16.45万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
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：
2015-08-10 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8970378
关键词：
Accounting Address Affect African American Age Autoantibodies Autoimmune Diseases Autoimmune Responses Autoimmunity Biological Markers Blood Chronic Clinical Communities DNA Data Development Diagnosis Diet Disease Environment Environmental Exposure Environmental Pollution Environmental Risk Factor Epitopes Equilibrium Etiology Feces First Degree Relative Food Frequencies Funding Future Generations Genes Genetic Predisposition to Disease Genomics Genotype Grant Heavy Metals Hour Immune Immunologics Incidence Individual Inflammatory Intervention Metagenomics Microbe Modeling Modification Organ Participant Pathogenesis Pathway interactions Patients Pharmaceutical Preparations Phenotype Play Population Prevalence Production Questionnaires Research Risk Factors Role Sampling Severities Smoking Specificity Structure Susceptibility Gene Systemic Lupus Erythematosus Talents Testing Trust United States National Institutes of Health Variant Whole-Genome Shotgun Sequencing Woman Work cost genetic variant gut microbiota high throughput analysis metagenome microbial microbial community microbiome pollutant pre-clinical public health relevance risk variant sex trait young woman

项目摘要

DESCRIPTION (provided by applicant): Systemic lupus erythematosus (SLE) is a chronic and potentially severe autoimmune disease which disproportionately affects women and African Americans (AA). Despite the role of environmental factors in modulating autoimmunity pathogenesis, the specific mechanisms by which it acts remain poorly understood. A growing body of evidence implicates the gut microbiota in the development of autoimmune disorders. In this study we will characterize the microbial composition (microbiome) and gene content (metagenome) of fecal DNA from samples obtained from AA patients with SLE, their unaffected first-degree relatives who show signs of autoimmunity, and healthy, unrelated, autoantibody-negative AA controls. The overall hypothesis of this proposal is that there is gut microbial variation at both the structural and functional level between individuals that influences development of autoimmunity and autoimmune disease. We will test this hypothesis by accomplishing 3 Specific Aims: 1) Testing the hypothesis that gut community structure (microbiome) correlates with markers of autoimmunity and SLE disease. 2) Testing the hypothesis that the microbiome's genes, variants and functional capabilities (metagenome) are associated with autoimmunity and SLE disease. 3) Testing the hypothesis that the gut microbial composition correlates with markers of autoimmunity and SLE disease in a multivariate model, taking into account host genotype data, phenotypic traits, diet and other exposures. Upon completion of these Aims we will have systematically identified bacterial biomarkers (e.g. SNPs, genes, strains) that correlate with SLE, can be investigated in other autoimmune diseases, and serve as potential targets for disease treatment.

描述（由适用提供）：全身性红斑狼疮（SLE）是一种慢性且可能严重的自身免疫性疾病，对妇女和非裔美国人（AA）的影响不成比例。尽管环境因素在调节自身免疫发病机理中的作用，但其起作用的特定机制仍然很熟悉。越来越多的证据表明，肠道菌群在自身免疫性疾病的发展中。在这项研究中，我们将表征从AA患者获得的样品的微生物组成（微生物组）和基因含量（元基因组），他们未受影响的一级亲戚，他们显示出自身免疫的迹象，健康，健康，无关，无关，自抗体抗体抗体抗体抗体AA控制。该提议的总体假设是，在影响自身免疫和自身免疫性疾病发展的个体之间的结构和功能水平上都存在肠道微生物变化。我们将通过完成3个具体目的来检验这一假设：1）检验肠道群落结构（微生物组）与自身免疫和SLE病的标记相关的假设。 2）检验微生物组的基因，变体和功能能力（元基因组）的假设与自身免疫性和SLE病有关。 3）测试肠道微生物组合物在多元模型中与自身免疫和SLE病的标记相关的假设，考虑到宿主基因型数据，表型性状，饮食和其他暴露。这些目标完成后，我们将在其他自身免疫性疾病中进行系统地鉴定出与SLE相关的细菌生物标志物（例如SNP，基因，菌株），并作为疾病治疗的潜在靶标。