Gut Microbiota in Patients with Multiple Sclerosis

描述(申请人提供)：目前正在探索的了解健康和疾病中的免疫系统的主要努力之一是对人类微生物群的调查。在多发性硬化症动物模型中的大量研究表明，肠道微生物区系与触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试点研究，以确定MS患者肠道微生物组是否存在差异，以及肠道微生物组是否在治疗过程中发生任何变化。我们发现MS中来自古生界的微生物数量显著增加，与治疗相关的肠道微生物群也发生了变化。据我们所知，这是多发性硬化症肠道微生物群变化的第一次展示。我们调查的重点是扩大研究的患者数量，包括疾病进行性形式的患者，对治疗前后的患者进行纵向研究，并进行免疫学检查，以了解古细菌对多发性硬化症免疫功能的影响方式。我们假设肠道微生物群的变化与多发性硬化症的易感性和免疫变化以及治疗反应有关。目的1.调查初治MS患者肠道菌群情况，包括CIS、复发缓解期和继发性进展期MS。目的2.研究治疗对MS肠道微生物群的影响。目的3.探讨MS患者肠道微生物群中的古生菌与免疫功能的关系。为了进行我们的研究，我们将利用在合作伙伴多发性硬化症中心跟踪的大量特征良好的多发性硬化症患者，作为攀登纵向观察研究的一部分，以及布里格姆妇女医院的临床和翻译元基因组学中心。

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.