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Interactions Between Host Genetics and the Gut Microbiome in CNS Autoimmunity

中枢神经系统自身免疫中宿主遗传学与肠道微生物组之间的相互作用

基本信息

批准号：
10093145
负责人：
Dimitry N Krementsov
金额：
$ 34.13万
依托单位：
UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-03-15 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10093145
关键词：
16S ribosomal RNA sequencing Address Affect Animal Model Antibiotic Therapy Autoimmune Autoimmune Diseases Axon Bacteria CNS autoimmune disease CNS autoimmunity Central Nervous System Diseases Chromosomes Clinical Collection Complex Consomic Strain Data Demyelinations Developed Countries Diagnostic Disease Disease susceptibility Ecosystem Environment Environmental Risk Factor Etiology Evaluation Exhibits Experimental Autoimmune Encephalomyelitis Female Fostering Gene Expression Genes Genetic Genetic Variation Genetic study Germ-Free Gliosis Goals Health Healthcare Housing Human Immune Incidence Individual Inflammatory Intestines Laboratory mice Link Maps Modeling Mouse Strains Multiple Sclerosis Mus Neurologic Neurologic Dysfunctions Outcome Phenotype Physiology Play Population Predisposition Prevalence Risk Risk Factors Role Severities Shapes System Testing Therapeutic Variant Work care burden congenic consomic disability disorder risk dysbiosis epidemiology study experimental study frontier gene environment interaction genome-wide gut colonization gut microbiome gut microbiota human disease male microbiome microbiome composition microbiota microbiota transplantation microorganism mouse genetics multiple sclerosis patient neuroinflammation next generation novel rate of change segregation sex tool transmission process young adult

项目摘要

Project Summary Multiple sclerosis (MS) is a devastating autoimmune neuroinflammatory disease with a strikingly increasing incidence world-wide, implicating the influence of environmental factors. While genetics of MS are beginning to be understood, they can account for at most ~30% of the disease risk. The remainder of the disease risk is accounted for by environmental factors and gene-by-environment (G×E) interactions. Mechanisms of G×E in MS are not well understood, and are difficult to study in humans. Mounting evidence implicates a novel environmental risk factor for MS: dysregulation of the gut microbiome. In this application, we propose to take a genome-wide approach to identify gene × microbiome interactions in a novel and powerful mouse genetics system. These studies cannot be carried out in humans, and they will provide important mechanistic understanding of G×E in autoimmune disease of the CNS, and deliver cause vs. effect distinctions that are lacking in epidemiologic studies.

项目概要多发性硬化症（MS）是一种破坏性的自身免疫性神经炎症性疾病，其发病率急剧增加世界范围内的发病率，涉及环境因素的影响。虽然多发性硬化症的遗传学已开始可以理解的是，它们最多可占疾病风险的 30% 左右。其余的疾病风险是由环境因素和基因与环境（G×E）相互作用来解释。 G×E 的机制多发性硬化症目前还没有被很好地理解，并且很难在人类身上进行研究。越来越多的证据暗示一部小说 MS 的环境危险因素：肠道微生物组失调。在此应用中，我们建议采取全基因组方法来识别新型且强大的小鼠遗传学中基因×微生物组的相互作用系统。这些研究无法在人体中进行，但它们将提供重要的机制了解中枢神经系统自身免疫性疾病中的 G×E，并提供因果区别缺乏流行病学研究。