The role of gut microbiota in shaping the immune response in relapse-remitting and chronic-progressive mouse models of multiple sclerosis

Abstract

Abstract In this study, we used a mouse model of multiple sclerosis (MS), experimental autoimmune encephalitis (EAE), to evaluate the role of gut microbiota in modulating T helper cell function in chronic-progressive (CP) versus relapse-remitting (RR) forms of the disease. We hypothesized that encephalitogenic T cell function in RR-EAE and CP-EAE is differentially shaped by gut microbiota. Metagenomic sequencing of the variable V4 region of the prokaryotic 16S ribosomal RNA gene present in feces derived from naïve mice and mice exhibiting CP-EAE or RR-EAE revealed significantly diverse microbial populations, which may be responsible for differing disease courses. Specifically, the order Bacteroidales was dominantly represented by RR-EAE mice, with very little or no detection in naive or CP-EAE mice, suggesting a potential role for bacteria in this order in shaping tolerant or remittance-favoring conditions. Additionally, Akkermansia and rc4-4, of phyla Verrucomicrobia and Firmicutes, respectively, were identified specifically in CP-EAE, suggesting a potential pathogenic or pro-inflammatory role for bacteria belonging to these taxa, at least in the context of EAE. We performed qRT-PCR in order to test the validity of the sequencing findings, as well as used a gas chromatograph configured with flame-ionization detectors to evaluate short chain fatty acids from cecal flushes. The current study implies a role for gut microbiota in differentially shaping the immune response in models of RRMS and CPMS. Information regarding tolerance–promoting or –inhibiting conditions shaped by gut bacteria can be harnessed for the potential development of therapies for diseases possessing important inflammatory components.