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Gut dysbiosis in NMOSD promotes CNS autoimmunity

Conference
MS Virtual 2020

Neuromyelitis optica spectrum disorders (NMOSD) faecal microbiota increases susceptibility for experimental autoimmune encephalomyelitis (EAE) in a rodent model [1]. Reduction in the number of regulatory T cells may contribute to EAE exacerbation.

Dysbiosis of gut microbiota has been shown both in MS and NMOSD, suggesting that the gut microbiome may regulate inflammatory responses. A San Francisco-based group hypothesised that the gut microbiota from NMOSD patients play a role in NMOSD pathogenesis. To investigate this, they colonised wild-type C57BL/6 germ-free mice with faecal samples from an untreated NMOSD patient (n=10), a household healthy control (HHC; n=9), or vehicle (n=13) for 5 weeks. In the month after that, susceptibility to MOG p35-55-induced EAE was evaluated.

Results showed that EAE was more severe in mice colonised with faecal microbiota from NMOSD and HHC (3.1 and 2.6, respectively) than in mice from the vehicle group (1.9; P≤0.01). The mean clinical score of mice colonised with NMOSD gut microbiota was significantly higher than mice colonised with gut microbiota from HHC or vehicle (P≤0.001). The amount of CD4+Foxp3+CD25+ regulatory T cells was decreased in lamina propria of small (LP-SI) and large (LP-LI) intestine, Peyer’s patches, and mesenteric lymph node compartments in the NMOSD and HHC groups versus the vehicle group (P≤0.01). The amount of CD4+Foxp3+Helios+ T cells was significantly decreased in mesenteric lymph nodes and LP-SI in the NMOSD and HHC groups compared to the vehicle group (P≤0.01).

These results suggest that different mechanisms may be involved in EAE enhancement in NMOSD and HHC. The researchers intend to test more samples of NMOSD patients and healthy controls; to extract tissues and phenotype immune cells at the peak of the disease; and to perform 16sRNA analysis, to correlate bacterial compositions between samples and immunophenotyping of different tissues.

  1. Moinfar Z, et al. Gut dysbiosis in neuromyelitis optica promotes CNS autoimmunity. MSVirtual 2020, Abstract PS10.05.

 



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