16S rRNA sequences of gut microbiome and meta data

<p><b>Objective:</b>To understand the role of gut microbiome in influencing the pathogenesis of neuromyelitis optica spectrum disorders (NMOSD)among patients of south Indian origin.</p> <p><b>Methods:</b>In this case control study, stool and blood samples were collected from 39 NMOSD patients, including 17 with aquaporin 4 IgG antibodies (AQP4+) and 36 matched controls. 16S rRNA sequencing was used to investigate the gut microbiome. Peripheral CD4+ T cells were sorted in 12 healthy controls &amp; 12 AQP4+NMOSD patients, RNA extracted, and immune gene expression analyzed using Nanostring nCounter human immunology kit code set.</p> <p><b>Results: </b>Microbiota community structure (beta-diversity) differed between AQP4+ NMOSD and healthy controls (p &lt;0.001, pairwise PERMANOVA test). Linear discriminatory analysis effect size (LEfSe) identified several members of the microbiota that were altered in NMOSD patients, including an increase in <i>Clostridium bolteae </i>(effect size 4.23, pvalue 0.00007). <i>C.bolteae </i>was significantly more prevalent (p=0.02) amongAQP4-IgG + NMOSD (n= 8/17 subjects)compared to seronegative patients (n= 3/22) and was absent among healthy stool samples.<i>C bolteae </i>has a highly conserved glycerol uptake facilitator and related aquaporin protein(p59-71) that shares sequence homology with AQP4 peptide(p92-104), positioned within an immunodominant (AQP4specific)T cell epitope (p91-110).Presence of <i>C. bolteae</i> correlated with expression of inflammatory genes associated with both innate and adaptive immunity and particularly involved in plasma cell differentiation ,B cell chemotaxis and Th17 activation.</p> <p><b>Conclusion: </b>Our study described elevated levels of <i>C. bolteae </i>associated with AQP4+ NMOSD among Indian patients. It is possible that this organism may be causally related to the immunopathogenesis of this disease in susceptible individuals.</p> <p><b>Objective:</b>To understand the role of gut microbiome in influencing the pathogenesis of neuromyelitis optica spectrum disorders (NMOSD)among patients of south Indian origin.</p> <p><b>Methods:</b>In this case control study, stool and blood samples were collected from 39 NMOSD patients, including 17 with aquaporin 4 IgG antibodies (AQP4+) and 36 matched controls. 16S rRNA sequencing was used to investigate the gut microbiome. Peripheral CD4+ T cells were sorted in 12 healthy controls &amp; 12 AQP4+NMOSD patients, RNA extracted, and immune gene expression analyzed using Nanostring nCounter human immunology kit code set.</p> <p><b>Results: </b>Microbiota community structure (beta-diversity) differed between AQP4+ NMOSD and healthy controls (p &lt;0.001, pairwise PERMANOVA test). Linear discriminatory analysis effect size (LEfSe) identified several members of the microbiota that were altered in NMOSD patients, including an increase in <i>Clostridium bolteae </i>(effect size 4.23, pvalue 0.00007). <i>C.bolteae </i>was significantly more prevalent (p=0.02) amongAQP4-IgG + NMOSD (n= 8/17 subjects)compared to seronegative patients (n= 3/22) and was absent among healthy stool samples.<i>C bolteae </i>has a highly conserved glycerol uptake facilitator and related aquaporin protein(p59-71) that shares sequence homology with AQP4 peptide(p92-104), positioned within an immunodominant (AQP4specific)T cell epitope (p91-110).Presence of <i>C. bolteae</i> correlated with expression of inflammatory genes associated with both innate and adaptive immunity and particularly involved in plasma cell differentiation ,B cell chemotaxis and Th17 activation.</p> <p><b>Conclusion: </b>Our study described elevated levels of <i>C. bolteae </i>associated with AQP4+ NMOSD among Indian patients. It is possible that this organism may be causally related to the immunopathogenesis of this disease in susceptible individuals.</p>