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Benef Microbes. 2018 Apr 25;9(3):495-513. doi: 10.3920/BM2017.0116. Epub 2018 Jan 30.

Variations in diet cause alterations in microbiota and metabolites that follow changes in disease severity in a multiple sclerosis model.

Author information

1
1 Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East, 2600 EEJMRB, Salt Lake City, UT 84112, USA.
2
4 Baylor College of Medicine, Division of Abdominal Transplantation, Neurosensory Center, Houston, TX 77030, USA.
3
2 Department of Biochemistry and Metabolomics Core, University of Utah, 15 North Medical Drive East, A306 EEJMRB, Salt Lake City, UT 84112, USA.
4
3 uBiota LLC, 825 N 300 W STE: NE-200, Salt Lake City, UT 84103, USA.

Abstract

Multiple sclerosis (MS) is a metabolically demanding disease involving immune-mediated destruction of myelin in the central nervous system. We previously demonstrated a significant alteration in disease course in the experimental autoimmune encephalomyelitis (EAE) preclinical model of MS due to diet. Based on the established crosstalk between metabolism and gut microbiota, we took an unbiased sampling of microbiota, in the stool, and metabolites, in the serum and stool, from mice (Mus musculus) on the two different diets, the Teklad global soy protein-free extruded rodent diet (irradiated diet) and the Teklad sterilisable rodent diet (autoclaved diet). Within the microbiota, the genus Lactobacillus was found to be inversely correlated with EAE severity. Therapeutic treatment with Lactobacillus paracasei resulted in a significant reduction in the incidence of disease, clinical scores and the amount of weight loss in EAE mice. Within the metabolites, we identified shifts in glycolysis and the tricarboxylic acid cycle that may explain the differences in disease severity between the different diets in EAE. This work begins to elucidate the relationship between diet, microbiota and metabolism in the EAE preclinical model of MS and identifies targets for further study with the goal to more specifically probe the complex metabolic interaction at play in EAE that may have translational relevance to MS patients.

KEYWORDS:

experimental autoimmune encephalomyelitis; metabolomics; microbiome; myelin oligodendrocyte glycoprotein

PMID:
29380645
PMCID:
PMC5918152
DOI:
10.3920/BM2017.0116
[Indexed for MEDLINE]
Free PMC Article

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