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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要吉兰-巴利综合征（GBS）已成为低收入和中等收入人群的主要健康负担后脊髓灰质炎时代后的国家（中低收入国家）GBS 的预后在过去两年中没有改善。几十年来，我们的研究小组已经证明了 GBS 的发病率、疾病严重程度和死亡率。与发达国家相比，孟加拉国的发病率更高，但我们对造成这种情况的因素知之甚少。我们的目标是确定中低收入国家 GBS 患者的疾病发病机制和严重程度的影响。 GBS 患者肠道微生物组中富含厚壁菌门的物种并确定其调节宿主微生物组施加的 T 和 B 细胞反应当前的主要假设。该项目是肠道微生物组是否在细胞免疫反应的调节中发挥着至关重要的作用在 GBS 发病过程中，我们的具体目标将检验以下假设：具体目标#1：我们将识别并比较肠道微生物组中厚壁菌门的物种 GBS 患者与无并发症的空肠弯曲菌肠炎患者的对照和相关性 GBS 患者肠道微生物参与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组对 T 细胞和 B 细胞分化的调节，以预测免疫疾病进展期间的耐受性并确定与 GBS 严重程度的关联。目前的项目是中低收入国家首次尝试寻找宿主肠道微生物组因素这项研究将是一项针对高收入和中等收入人群的合作项目。国家（UMIC）和 LMIC 探索这种长期神经系统疾病的发病机制本探索性/发展拨款申请中提出的目标是建立在其基础上的。 icddr,b（孟加拉国）、Erasmus MC、大学医学中心（荷兰鹿特丹）、加州大学（戴维斯，美国）、约翰·霍普金斯大学（美国巴尔的摩）和国家神经科学研究所医院（孟加拉国达卡）这项探索性研究将成为了解肠道的路线图。 GBS 免疫发病机制中的微生物组调节并确定潜在的治疗靶点未来。