Author Of 1 Presentation
PS10.05 - Gut dysbiosis in neuromyelitis optica promotes CNS autoimmunity
Abstract
Background
Neuromyelitis optica (NMO) is a severe demyelinating disease of the central nervous system (CNS) causing irreversible neurological damage. Initial analyses of gut microbiota in NMO, multiple sclerosis and healthy controls (HHC) revealed dysbiosis in the NMO group, suggesting that the gut microbiome may regulate inflammatory responses
Objectives
We hypothesized that gut microbiota from NMO patients may participate and promote inflammatory responses in NMO pathogenesis.
Methods
Wild-type (WT) C57BL/6 germ-free mice were colonized with fecal samples from one untreated NMO patient (n = 10), one household HC (HHC) (n = 9) or vehicle (n = 13) for five weeks and then examined for susceptibility to MOG p35-55-induced experimental autoimmune encephalomyelitis (EAE) for 30 days post immunization. Upon termination of the study, lymphocytes from spleen, lamina propria of small (LP-SI) and large (LP-LI) intestine, mesenteric lymph nodes (MLN), Peyer’s patches (PP), brain, and spinal cord were examined for the expression of IL-17, IFN-γ, Foxp3, CD25, RORγt and Helios.
Results
In comparison to the mean EAE score of the vehicle group (1.9 ± 0.3), severity was greater (p ≤ 0.01) in mice colonized with fecal microbiota from NMO (3.1 ± 0.8) and HHC (2.7 ± 0.7). The mean clinical score of mice colonized with NMO gut microbiota was significantly greater than mice colonized with gut microbiota from HHC or vehicle (p ≤ 0.001). The frequency of CD4+Foxp3+CD25+ cells was decreased in LP-SI, LP-LI, PP and MLN compartments in NMO and HHC compared with vehicle group (p ≤ 0.01). CD4+Foxp3+Helios+ (another regulatory T cell subpopulation) was significantly decreased in MLN and LP-SI of NMO and HHC compared to vehicle group (P ≤ 0.01).
Conclusions
Our data suggest that NMO fecal microbiota increases EAE susceptibility. Reduction in frequency of Tregs in the gut of mice colonized with NMO fecal material may contribute to EAE exacerbation. Further analysis of microbiota and lymphocyte populations in mice colonized with fecal material from NMO and HHC samples are needed. Results from our ongoing study should provide valuable insight regarding the potential role of gut microbiota in NMO.