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16S rRNA sequences of gut microbiome and meta data

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Sep 18, 2021 version files 1.49 GB

Abstract

Objective:To understand the role of gut microbiome in influencing the pathogenesis of neuromyelitis optica spectrum disorders (NMOSD)among patients of south Indian origin.

Methods: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 & 12 AQP4+NMOSD patients, RNA extracted, and immune gene expression analyzed using Nanostring nCounter human immunology kit code set.

Results: Microbiota community structure (beta-diversity) differed between AQP4+ NMOSD and healthy controls (p <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 Clostridium bolteae (effect size 4.23, pvalue 0.00007). C.bolteae 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.C bolteae 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 C. bolteae 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.

Conclusion: Our study described elevated levels of C. bolteae 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.

Objective:To understand the role of gut microbiome in influencing the pathogenesis of neuromyelitis optica spectrum disorders (NMOSD)among patients of south Indian origin.

Methods: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 & 12 AQP4+NMOSD patients, RNA extracted, and immune gene expression analyzed using Nanostring nCounter human immunology kit code set.

Results: Microbiota community structure (beta-diversity) differed between AQP4+ NMOSD and healthy controls (p <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 Clostridium bolteae (effect size 4.23, pvalue 0.00007). C.bolteae 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.C bolteae 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 C. bolteae 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.

Conclusion: Our study described elevated levels of C. bolteae 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.