Gut Microbiota Changes in Experimental Autoimmune Encephalomyelitis and Cuprizone Mice Models

ACS Chem Neurosci. 2021 Mar 3;12(5):893-905. doi: 10.1021/acschemneuro.0c00695. Epub 2021 Feb 10.

Abstract

Multiple sclerosis (MS) is a chronic and neurodegenerative disease of the central nervous system (CNS) characterized by the immune mediated attack on axons and the subsequent demyelination. There is growing evidence that the gut microbiota of MS patients is altered; however, the connection between demyelination events and changes in the gut microbiota has not been determined. The objective of the current work was to characterize the microbial dysbiosis in two murine demyelinating models and to study the correlation between them. Concurrently, their suitability as predictors of microbial changes in MS patients was assessed. To this purpose, experimental autoimmune encephalomyelitis (EAE) and cuprizone (CPZ) models were induced in C57BL/6 mice that were monitored for 4 and 9 weeks, respectively. Fecal samples were collected during disease progression. Motor skill performance was evaluated by EAE scale measurement in EAE mice and demyelination by magnetic resonance imaging (MRI) in CPZ ones. EAE and CPZ mice revealed drastic microbial changes according to disease progression, adding a new layer of complexity to the understanding of demyelination and remyelination processes. Besides, the reported microbial changes replicate most of the characteristics that define the potential dysbiosis in MS patients. The controlled environment and stable diet that animals have in research centers offer an exceptional scenario to modify animal's microbiota and provide opportunities to study host microbiota interplay with restrained conditions not achievable in human studies. Nevertheless the slight differences from murine model's and patient's microbiota should be considered in the design of studies aiming to modulate the microbiota.

Keywords: EAE; Microbiota; cuprizone model; demyelination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cuprizone / toxicity
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental*
  • Gastrointestinal Microbiome*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis*
  • Neurodegenerative Diseases*

Substances

  • Cuprizone