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

项目摘要 格林-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低收入国家。GBS的预后在过去两年中没有改善 几十年我们的研究小组先前表明，GBS的发病率、疾病严重程度和死亡率 与发达国家相比，孟加拉国的死亡率更高。人们对这些因素知之甚少， 影响LMIC中GBS患者疾病发病机制和严重程度。我们的目标是找出 GBS患者肠道微生物组中厚壁菌门丰富的物种，并确定其调控 T和B细胞的反应。当前的主要假设是 肠道微生物组是否在细胞免疫反应的调节中起着至关重要的作用 在GBS的发病过程中。我们的具体目标将测试以下假设： 目标#1：我们将识别和比较肠道微生物组中厚壁菌门的物种 GBS患者与无并发症空肠弯曲菌肠炎对照组的比例， GBS患者肠道微生物参与和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和B细胞分化的调节， 疾病进展期间的耐受性，并确定与GBS严重程度的关联。的 目前的项目是LMIC首次尝试寻找宿主肠道微生物组因子， GBS患者。这项研究将是上层和中层收入者之间的一项合作倡议， 国家（UMIC）和LMIC，以探索这种长期神经系统疾病的发病机制。 disorder.在这个探索性/发展性赠款申请中提出的目标是建立在 国际复员方案理事会B（孟加拉国）、伊拉斯谟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（巴尔的摩，美国）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 日后

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.