Gut Microbiota in Patients with Multiple Sclerosis

多发性硬化症患者的肠道微生物群

• 批准号: 9333436
• 负责人: Howard L Weiner
• 金额: $ 38.83万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9333436
• 关键词: Address; Affect; Aftercare; Animal Model; Archaea; Blood; CNS autoimmunity; Clinical; Coupled; Data; Disease; Grant; Health; Hospitals; Human Microbiome; Immune; Immune System Diseases; Immune System and Related Disorders; Immune response; Immune system; Immunologics; Individual; Investigation; Laboratories; Link; Longitudinal observational study; Magnetic Resonance Imaging; Measurable; Metagenomics; Methodology; Organism; Patients; Pilot Projects; Predisposition; Relapse; Sampling; Severity of illness; Societies; United States National Institutes of Health; Woman; base; cohort; comparison group; gut microbiome; gut microbiota; immune activation; immune function; interest; microbiome; multiple sclerosis patient; novel therapeutics; public health relevance; response; treatment effect; treatment response

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.

描述（由申请人提供）：目前正在探索了解健康和疾病中的免疫系统的主要努力之一是研究人类微生物组。在MS动物模型中的许多研究暗示肠道微生物群触发CNS自身免疫。我们对肠道免疫系统有着长期的兴趣，我们重新开始了一项试点研究，以确定MS患者的肠道微生物组是否存在差异，以及肠道微生物组是否发生了与治疗相关的任何变化。我们发现，MS中来自微生物王国的微生物丰度显著增加，并且肠道微生物组发生了与治疗相关的变化。据我们所知，这是第一次证明MS肠道微生物组的变化。我们研究的重点是扩大研究的患者数量，包括疾病进展形式的患者，以纵向方式研究治疗前后的患者，并进行免疫学调查，以了解肠道影响MS免疫功能的方式。微生物组与MS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、复发缓解型和继发性进行性MS）中的肠道微生物组。研究治疗对MS肠道微生物组的影响。目的3。研究MS患者肠道微生物组中的葡萄球菌与免疫功能的联系。为了进行我们的研究，我们将利用合作伙伴MS中心随访的大量特征良好的MS患者，作为CLIMB纵向观察性研究的一部分，以及布里格姆妇女医院的临床和转化宏基因组学中心。