Gut Microbiota in Patients with Multiple Sclerosis

描述（由申请人提供）：目前正在探索的了解免疫系统在健康和疾病中的主要努力之一是对人类微生物组的研究。在多发性硬化症动物模型中进行的大量研究表明，肠道微生物群与引发中枢神经系统自身免疫有关。我们对肠道免疫系统有长期的兴趣，我们重新开始了一项初步研究，以确定多发性硬化症患者肠道微生物组是否存在差异，以及肠道微生物组的任何变化是否与治疗有关。我们发现多发性硬化症中来自古细菌王国的生物体丰度显著增加，并且与治疗相关的肠道微生物组发生了变化。据我们所知，这是ms患者肠道微生物组变化的首次证明。我们调查的重点是扩大研究的患者数量，包括患有进行性疾病的患者，以纵向方式研究患者治疗前后。我们假设肠道微生物组的变化与多发性硬化症的易感性和免疫变化以及对治疗的反应有关。目的1。研究未经治疗的多发性硬化症患者的肠道微生物组，包括CIS、复发缓解型和继发性进展型多发性硬化症。探讨治疗对ms - Aim 3患者肠道微生物组的影响。探讨多发性硬化症患者肠道菌群中古生菌与免疫功能的联系。为了开展我们的研究，我们将利用伙伴多发性硬化症中心作为CLIMB纵向观察研究和布里格姆妇女医院临床与转化宏基因组学中心的一部分跟踪的大量特征明确的多发性硬化症患者。

DESCRIPTION (provided by applicant): One of the major efforts currently being explored to understand the immune system in health and disease is investigation of the human microbiome. Numerous studies in animal models of MS implicate the microbiota of the gut in triggering CNS autoimmunity. We have had a long-term interest in the gut immune system and we reembarked on a pilot study to determine if differences in the gut microbiome existed in MS patients and whether any changes in the gut microbiome occurred in association with treatment. We found a significant increase in abundance of organisms from the Archaea kingdom in MS and changes in the gut microbiome associated with treatment. To our knowledge, this is the first demonstration of changes in the gut microbiome in MS. The focus of our investigations are to expand the numbers of patients studied, include patients with the progressive form of the disease, to study patients in a longitudinal fashion before and after treatment, and to perform immunologic investigations to understand the manner in which Archaea affects immune function in MS. We hypothesize that changes in the gut microbiome are linked to susceptibility and immune changes that occur in MS as well as response to treatment. Aim 1. Investigate the gut microbiome in untreated MS subjects including CIS, relapsing- remitting and secondary progressive MS. Aim 2. Investigate the effect of treatment on the gut microbiome in MS. Aim 3. Investigate the linkage of Archaea in the gut microbiome of MS patients to immune function. To perform our studies, we will take advantage of the large cohort of well characterized MS patients followed at the Partners MS Center as part of the CLIMB longitudinal observational study and the Center for Clinical and Translational Metagenomics at the Brigham and Women's Hospital.