The gut microbiome affects the progression of disease in a murine model of secondary progressive MS
Author(s): ,
J Ochoa-Reparaz
Affiliations:
Biology, Eastern Washington University, Cheney, WA
,
E Kasper
Affiliations:
Microbiology/Immunology, Dartmouth Medical School, Hanover, NH, United States
,
S Colpitts
Affiliations:
Microbiology/Immunology, Dartmouth Medical School, Hanover, NH, United States
L Kasper
Affiliations:
Microbiology/Immunology, Dartmouth Medical School, Hanover, NH, United States
ECTRIMS Online Library. Kasper L. 09/15/16; 146305; P465
Lloyd Kasper
Lloyd Kasper
Contributions
Abstract

Abstract: P465

Type: Poster

Abstract Category: Pathology and pathogenesis of MS - Progressive MS

Background and objective: Recent findings reveal the importance of gut microbes in the development of experimental models of CNS inflammatory demyelination. We demonstrated that gut microbes and in particular the symbiont factor polysaccharide-A (PSA) produced by Bacteroides fragilis significantly influence gut immune responses and drive protection in relapsing-remitting EAE. Furthermore, in mice with EAE, onset of disease promotes significant changes in the intestinal permeability due to molecular modifications in the epithelial tight junctions, and changes in gut microbial abundances have been observed in MS patients when compared with healthy individuals. These observations suggest that the host-microbiota interaction is bi-directional. We propose that immunological changes that occur during disease modify the composition of the gut microbiome.

Methods:
We hypothesized that the gut microbiota relative abundances differ between the acute inflammatory and chronic progressive stages of a murine model of secondary-progressive MS (SP-EAE). We compared the gut microbiome in the EAE model of Non-Obese Diabetic (NOD) mice with non-EAE mice. The NOD model shows a bi-phasic pattern of disease that more closely resembles the human condition (RR-MS transitioning to SP-MS). In addition, we evaluated whether treatment with a cocktail of broad-spectrum antibiotics and the treatment with PSA would modify the outcome of the progressive stage of EAE in NOD mice.

Results: Results showed that the trend of the mortality and the clinical scores of mice treated with antibiotics, as well as with oral treatment with PSA, were reduced when compared to untreated EAE NOD mice.

Conclusions:
Results obtained in this work support the hypothesis that there is a reciprocal effect of experimental CNS inflammatory demyelination on the modification of the microbiome. Our studies provide the foundation to determine whether therapeutic intervention in the gut might be beneficial in terms of disease progression.

Disclosure: Project funded by a NMSS pilot grant.

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