Interactions Between Host Genetics and the Gut Microbiome in CNS Autoimmunity

项目摘要 多发性硬化症（MS）是一种破坏性自身免疫性神经炎性疾病， 全球范围内的发病率，涉及环境因素的影响。虽然MS的遗传学开始 但是，它们最多可以占疾病风险的30%。其余的疾病风险是 由环境因素和基因与环境（G×E）的相互作用解释。G×E的机制 MS还没有被很好地理解，并且很难在人类中进行研究。越来越多的证据表明 MS的环境风险因素：肠道微生物组失调。在本申请中，我们建议采用 全基因组方法在一种新的强大的小鼠遗传学中鉴定基因×微生物组相互作用 系统这些研究不能在人类中进行，它们将提供重要的机制。 了解G×E在中枢神经系统自身免疫性疾病中的作用，并提供 缺乏流行病学研究。

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.