Gut Microbiota in Patients with Multiple Sclerosis

描述（由申请人提供）：目前为了解健康和疾病中的免疫系统而探索的主要努力之一是对人类微生物组的研究。对多发性硬化症动物模型的大量研究表明，肠道微生物群会引发中枢神经系统自身免疫。我们对肠道免疫系统有着长期的兴趣，并重新开展了一项试点研究，以确定多发性硬化症患者的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相关。我们发现多发性硬化症中古生菌界的生物丰度显着增加，并且肠道微生物群与治疗相关的变化。据我们所知，这是多发性硬化症中肠道微生物组变化的首次证明。我们研究的重点是扩大研究的患者数量，包括患有疾病进展的患者，在治疗前后对患者进行纵向研究，并进行免疫学研究以了解古细菌影响多发性硬化症免疫功能的方式。我们假设肠道微生物组的变化与多发性硬化症中发生的易感性和免疫变化以及对治疗的反应有关。目标 1. 研究未经​​治疗的 MS 受试者（包括 CIS、复发缓解型和继发进展型 MS）的肠道微生物组。目标 2. 研究治疗对多发性硬化症肠道微生物组的影响。目标 3. 研究多发性硬化症患者肠道微生物组中的古细菌与免疫功能的联系。为了进行我们的研究，我们将利用在 Partners MS 中心（作为 CLIMB 纵向观察研究的一部分）和布莱根妇女医院临床和转化宏基因组学中心跟踪的大量特征明确的 MS 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.