Gut microbiome and regulation on immune responses in Guillain-Barre syndrome: a prospective controlled study

肠道微生物组和吉兰-巴利综合征免疫反应的调节：一项前瞻性对照研究

• 批准号: 10297902
• 负责人: Zhahirul Islam
• 金额: $ 13.43万
• 依托单位: INTERNATIONAL CTR/DIARRHOEAL DIS RES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10297902
• 关键词: Academic Medical Centers; Address; Applications Grants; Autoimmune Diseases; B cell differentiation; B cell repertoire; B-Lymphocyte Subsets; B-Lymphocytes; Bacteria; Baltimore; Bangladesh; California; Campylobacter jejuni; Cardiovascular system; Cells; Cellular biology; Chickens; Classification; Clinical Course of Disease; Controlled Study; DNA Library; DNA sequencing; Data; Developed Countries; Development; Disease; Disease Progression; Disease susceptibility; Environment; Environmental Risk Factor; Epidemiology; Exploratory/Developmental Grant; Firmicutes; Future; Gangliosides; Genes; Guillain Barré Syndrome; Health; Hospitals; Human; Immune; Immune Tolerance; Immune response; Immunity; Immunosuppression; Incidence; Individual; Infection; Infrastructure; Institutes; Integration Host Factors; Interferons; Interleukin-10; Interleukin-17; Interleukin-4; Interleukin-6; Intravenous Immunoglobulins; Libraries; Maps; Measures; Metagenomics; Molecular Mimicry; Muslim religion; Nerve; Netherlands; Neurosciences; Pathogenesis; Patients; Phenotype; Plasma Exchange; Play; Poliomyelitis; Predisposition; Prognosis; Reaction; Regulation; Regulatory T-Lymphocyte; Reporting; Research; Research Project Grants; Residual state; Role; Sampling; Severities; Severity of illness; Signal Transduction; System; Systemic Lupus Erythematosus; T cell differentiation; T cell regulation; T-Lymphocyte; TNF gene; Taxonomy; Testing; Universities; adaptive immune response; beta diversity; case control; cell growth regulation; cohort; commensal microbes; cost; cytokine; design; disability; enteritis; gut microbiome; gut microbiota; gut-brain axis; host microbiome; immunoregulation; insight; interleukin-22; interleukin-23; low and middle-income countries; member; microbial; microbial composition; mimicry; mortality; nervous system disorder; new therapeutic target; next generation sequencing; pathogen; prospective; response; skills; standard care; synthetic polymer Bioplex; therapeutic target

Project Summary Guillain-Barré syndrome (GBS) has become a major health burden in low- and middle-income countries (LMIC) after post-polio era. The prognosis of GBS has not improved over the last two decades. Our group previously showed that the incidence, disease severity and mortality of GBS are higher in Bangladesh compared to the developed world. Little is known about the factors that influence disease pathogenesis and severity in patients with GBS in LMIC. We aim to identify the Firmicutes rich species in gut microbiome in patients with GBS and determine the regulation of T and B cell responses imposed by the host microbiome. The main hypothesis of the current project is whether gut microbiome plays a vital role in regulation of the cellular immune response during the pathogenesis of GBS. Our specific aims will test the following hypotheses: Specific aim #1: we will identify and compare species from the Firmicutes phylum in the gut microbiome of patients with GBS versus uncomplicated Campylobacter jejuni enteritis controls and correlate between gut microbial involvement and disease severity in patients with GBS. Specific aim #2: we will determine gut microbiome regulation of T and B cell differentiation to predict immune tolerance during disease progression and identify the association with the severity of GBS. The current project is the very first attempt taken from LMIC to find the host gut microbiome factors of GBS patients. This study will be a collaborative initiative between upper and middle in-come countries (UMICs) and LMICs to explore the pathogenesis of such a long term neurological disorder. The aims proposed in this exploratory/developmental grant application is built upon ongoing, long-standing collaborative efforts between the icddr,b (Bangladesh), Erasmus MC, University Medical Centre (Rotterdam, the Netherlands), the University of California (Davis, USA), Johns Hopkins University (Baltimore, USA) and the National Institute of Neurosciences & Hospital (Dhaka, Bangladesh). This exploratory study will be the road map to understand the gut microbiome regulation in immune-pathogenesis of GBS and identify potential therapeutic targets in future.

项目摘要 格林-巴利综合征(GBS)已成为中低收入者的主要健康负担 小儿麻痹症后的国家(LMIC)。在过去的两年中，GBS的预后并没有改善。 几十年。我们小组先前的研究表明，GBS的发病率、疾病严重程度和死亡率 与发达国家相比，孟加拉国的这一比例更高。人们对这些因素知之甚少 影响LMIC中GBS患者的发病机制和严重程度。我们的目标是确定 GBS患者肠道微生物群中富含非米米特的菌群及其调控 宿主微生物群施加的T和B细胞反应。当前的主要假设是 项目是关于肠道微生物是否在调节细胞免疫反应中起重要作用。 在GBS的发病过程中。我们的具体目标将检验以下假设：具体 目标1：我们将在肠道微生物群中鉴定和比较来自Firmicuts门的物种 GBS患者与无并发症空肠弯曲菌肠炎的对照和相关性 GBS患者肠道微生物感染与疾病严重程度之间的关系。具体目标2： 我们将确定肠道微生物群对T和B细胞分化的调节以预测免疫 在疾病进展过程中的耐受性，并确定与GBS严重程度的关联。这个 目前的项目是从LMIC首次尝试发现宿主肠道微生物组因子 GBS患者。这项研究将是中上层收入者之间的一项合作倡议 各国(UMICs)和LMICs探讨这种长期神经系统的发病机制 无序。这项探索性/发展性赠款申请中提出的目标是建立在 解除武装、复员和重返社会国际委员会b(孟加拉国)、伊拉斯谟委员会、 大学医学中心(鹿特丹，荷兰)，加州大学(戴维斯， 美国)、约翰霍普金斯大学(美国巴尔的摩)和美国国家神经科学与科学研究所 医院(孟加拉国达卡)。这项探索性研究将是理解直觉的路线图 微生物组调控在GBS免疫发病机制中的作用及潜在治疗靶点的确定 在未来。