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.

Project Narrative: This research project will identify the Firmicutes rich species in gut microbiome in patients with Guillain-Barré syndrome (GBS) and determine the regulation of immune responses imposed by the host microbiome. The proposed study will provide new insight of gut-brain axis signaling to understand the role of gut microbiome through metagenomic approach and cellular expression of T and B cells repertoires, as well as correlate with clinical course and disease severity of GBS. The project will be a collaborative initiation between low- and middle-income countries (LMIC) and developed countries that enables to plan for mechanistic studies on gut microbiome regulation of immune responses for GBS patients to predict new therapeutic targets in future.