Advantages and limitations of experimental autoimmune encephalomyelitis in breaking down the role of the gut microbiome in multiple sclerosis

Abstract

Since the first model of experimental autoimmune encephalomyelitis (EAE) was introduced almost a century ago, there has been an ongoing scientific debate about the risks and benefits of using EAE as a model of multiple sclerosis (MS). While there are notable limitations of translating EAE studies directly to human patients, EAE continues to be the most widely used model of MS, and EAE studies have contributed to multiple key breakthroughs in our understanding of MS pathogenesis and discovery of MS therapeutics. In addition, insights from EAE have led to a better understanding of modifiable environmental factors that can influence MS initiation and progression. In this review, we discuss how MS patient and EAE studies compare in our learning about the role of gut microbiome, diet, alcohol, probiotics, antibiotics, and fecal microbiome transplant in neuroinflammation. Ultimately, the combination of rigorous EAE animal studies, novel bioinformatic approaches, use of human cell lines, and implementation of well-powered, age- and sex-matched randomized controlled MS patient trials will be essential for improving MS patient outcomes and developing novel MS therapeutics to prevent and revert MS disease progression.

Keywords: EAE; FMT; MS; alcohol; antibiotics; diet; gut microbiome; probiotics.

FIGURE 1

A myriad of experimental autoimmune encephalomyelitis (EAE) models have been developed to capture varied aspects of the clinical course of multiple sclerosis (MS) [C57BL/6 (B6), SJL/J, and PL/J mice]. Genetic models have allowed the study of T and B cells in MS in TCR and B-cell receptor (BCR) transgenics. Germ-free models have enabled the study of the gut microbiome. Viral models, such as Theiler’s murine encephalomyelitis virus (TMEV), have elucidated viral contribution to MS. MS-related demyelination and remyelination has been studied in cuprizone and lysolecithin models. Connexin knockouts have been used to study the role of the blood brain barrier (BBB) in neuroinflammation. Central tolerance has been examined in shiverer transgenic mice.