Gut micro biota in patients with multiple sclerosis

多发性硬化症患者的肠道微生物群

• 批准号: 8177205
• 负责人: Howard L Weiner
• 金额: $ 22.3万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8177205
• 关键词: Acute; Address; Affect; Animals; Antibiotics; Antigens; Autoantigens; Autoimmune Diseases; Autoimmune Process; Autoimmunity; Bacteria; Bacterial Antigens; Bifidobacterium; Biota; Blood; Brain; C57BL/6 Mouse; CD4 Positive T Lymphocytes; Clinical; Collaborations; Crohn' s disease; Dendritic Cells; Development; Diet; Disease; Doxycycline; Enhancing Lesion; Epidemiologic Studies; Equilibrium; Experimental Autoimmune Encephalomyelitis; Exploratory/Developmental Grant; Foundations; Genetic; Gut associated lymphoid tissue; Heat shock proteins; Helicobacter pylori; Human Microbiome; Immune; Immune system; Inbreeding; Infection; Inflammatory Bowel Diseases; Intestines; Investigation; Japanese Population; Lactobacillus; Lamina Propria; Lesion; Link; M cell; Magnetic Resonance Imaging; Measures; Modeling; Multiple Sclerosis; Mus; Myelin; Neurologic; Onset of illness; Pathogenesis; Patients; Play; Population; Probiotics; Recurrent disease; Regulatory T-Lymphocyte; Relapse; Relapsing-Remitting Multiple Sclerosis; Reporting; Research Personnel; Rheumatoid Arthritis; Role; Sampling; Seasonal Variations; Secondary Progressive Multiple Sclerosis; Secondary to; Shapes; Symptoms; T-Lymphocyte; Technology; Time; Ulcerative Colitis; arm; base; cytokine; disability; gut microbiota; insight; lymph nodes; microbiome; mouse model; nervous system disorder; novel; open label; osteopontin; peripheral tolerance; programs; young adult

DESCRIPTION (provided by applicant): Multiple sclerosis is an autoimmune disease thought to be caused by a dysregulation between effector T cells, including Th1/Th17 T cells, and regulatory T cells. The factors associated with MS including disease onset, relapses and progression are poorly understood, although epidemiological studies have suggested a role for diet, seasonal variation, infection, and genetic factors. We hypothesize that MS may be linked to the gut microbiome, as it is now becoming recognized that the gut microbiome may play a key role in shaping the immune repertoire and the balance between various effector and regulatory T cell populations. Nearly 80% of all T lymphocytes of the body are compartmentalized to the gut associated lymphoid tissues (GALT. It is becoming increasingly recognized that the gut may have a major influence on the systemic immune system. Although to date, the interface between the gut microbiome has not been extensively studied, relationships between the gut microbiome and autoimmune illness have been found. Most studies have been carried out in inflammatory bowel disease, though the effect of gut microbiota is not restricted to local autoimmune processes. The fecal microbiota in patients with rheumatoid arthritis differs from healthy controls. Studies on the microbiome and MS have been few. Japanese investigators suggest that H. pylori is a potential protective factor against MS in Japanese populations and Bifidobacteria have been reported decreased in MS. In the EAE mouse model of MS, probiotic administration of lactobacillus reduces disease activity and depletion of microflora using antibiotics in inbred SJL and C57BL/6 mice impaired the development of EAE, and that this protection was associated with a reduction of proinflammatory cytokines, potentially suggesting a role for induction of peripheral tolerance through alterations of gut commensals. They also reported positive effects on EAE in animals treated with gut components orally. We believe an investigation of the gut microbiome in MS is timely, and have established collaboration with the Broad Foundation which has a major program related to the Human Microbiome Project. We will address the following Specific Aims: 1. Do patients with relapsing remitting MS have differences in the gut microbiome compared to healthy controls? 2. Do patients with secondary progressive MS have differences in the gut microbiome compared to healthy controls and to relapsing-remitting MS? 3. Is there a link between immune signatures as measured by antigen arrays and other immune measures in the blood of MS patients (oxysterols, osteopontin, heat shock proteins) and the gut microbiome? In summary, we believe that the investigation of the gut microbiome in MS fits with the R21 mechanism as it is exploratory and novel and seeks to break ground towards new directions and applications. It applies for the first time an important newly developing technology to gain potential basic insights into an autoimmune disease whose underlying pathogenesis remains unknown. PUBLIC HEALTH RELEVANCE: Multiple sclerosis (MS) is a disease of the nervous system that affects young adults. The body's immune system plays a key role in MS and it is now recognized that the large number of bacteria in the gut can affect the immune system. We will be studying the gut flora in MS patients to determine if the gut flora is different in MS patients and is in some way linked to the disease.

描述（由申请人提供）：多发性硬化症是一种自身免疫性疾病，被认为是由效应T细胞（包括Th1/Th17 T细胞）和调节性T细胞之间的失调引起的。尽管流行病学研究表明饮食，季节性变异，感染和遗传因素的作用，但与MS有关的因素（包括疾病发作，复发和进展）尚不清楚。我们假设MS可能与肠道微生物组有关，因为现在已经认识到肠道微生物组在塑造免疫库以及各种效应子和调节性T细胞种群之间的平衡中可能起关键作用。人体所有T淋巴细胞中近80％都被隔离为相关的淋巴组织组织（Galt。越来越认识到，肠道可能对系统性免疫系统产生重大影响。尽管迄今为止，肠道微生物组之间的界面尚未被吞噬的肠道和自动远离肠内，但远距离远离了远程远程远程远程远程远程远程远程远程远程远程远程远程远程远程远程远程远程远程远程远程远离肠。疾病，肠道菌群的效果不限于粪便的自身免疫性。乳杆菌在近交SJL和C57BL/6小鼠中使用抗生素减少了疾病的活性和耗尽，损害了EAE的发展，并且这种保护与促炎细胞因子的降低相关，从而有可能通过促进肠外壳来诱导肠外壳的作用，从而促进了肠道的作用。口头，我们认为对MS的肠道微生物组进行了调查，并与广泛的基础建立了与人类微生物组项目相关的主要计划，我们将解决以下特定目标：1。与健康控制的患者相比，与Healthy Controls的差异相比MS 3。通过抗原阵列测量的免疫特征与MS患者的血液中的其他免疫措施（氧化酚，骨hoptepontin，热休克蛋白）和肠道微生物组中的联系首次是一项重要的新开发技术，可以获得对自身免疫性疾病的潜在基本见解，该疾病的基本发病机理仍然未知。 公共卫生相关性：多发性硬化症（MS）是影响年轻人的神经系统的一种疾病。人体的免疫系统在MS中起关键作用，现在已经认识到肠道中的大量细菌会影响免疫系统。我们将研究MS患者的肠道菌群，以确定MS患者的肠道菌群是否不同，并且与该疾病有关。