Abstract
Multiple sclerosis is a chronic inflammatory disease of the central nervous system (CNS). It is widely accepted that autoimmune response against the antigens of the CNS is the essential pathogenic force in the disease. It has recently become increasingly appreciated that activated encephalitogenic cells tend to migrate toward gut associated lymphoid tissues (GALTs) and that interrupted balance between regulatory and inflammatory immunity within the GALT might have decisive role in the initiation and propagation of the CNS autoimmunity. Gut microbiota composition and function has the major impact on the balance in the GALT. Thus, our aim was to perform analyses of gut microbiota in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Albino Oxford (AO) rats that are highly resistant to EAE induction and Dark Agouti (DA) rats that develop EAE after mild immunization were compared for gut microbiota composition in different phases after EAE induction. Microbial analyses of the genus Lactobacillus and related lactic acid bacteria showed higher diversity of Lactobacillus spp. in EAE-resistant AO rats, while some members of Firmicutes and Proteobacteria (Undibacterium oligocarboniphilum) were detected only in feces of DA rats at the peak of the disease (between 13 and 16 days after induction). Interestingly, in contrast to our previous study where Turicibacter sp. was found exclusively in non-immunized AO, but not in DA rats, in this study it was detected in DA rats that remained healthy 16 days after induction, as well as in four of 12 DA rats at the peak of the disease. Similar observation was obtained for the members of Lachnospiraceae. Further, production of a typical regulatory cytokine interleukin-10 was compared in GALT cells of AO and DA rats, and higher production was observed in DA rats. Our data contribute to the idea that gut microbiota and GALT considerably influence multiple sclerosis pathogenesis.
Highlights
Gut microbiota is an essential factor in development of cellular and humoral components of the gut associated lymphoid tissue (GALT) (Sommer and Bäckhed, 2013), while its dysbiosis have been correlated with various diseases (Carding et al, 2015)
Various bacteria and their products have been shown beneficial in EAE, for instance, B. fragilis and its capsular polysaccharide A, Salmonella typhimurium expressing the complete Freund’s adjuvant (CFA)/I fimbriae from E. coli, Bifidobacterium animalis, Lactobacillus spp. as well as a probiotic mixture of Lactobacillus spp. with Bifidobacterium bifidum and Streptococcus thermophilus
In order to determine possible microbial players responsible for alleviation of EAE symptoms in Dark Agouti (DA) rats as well as for the EAE-resistance of Albino Oxford (AO) rats, gut microbial diversity was characterized by denaturing gradient gel electrophoresis (DGGE) analysis of rDNA amplicons using DNA isolated from fecal samples as templates and Lab-0159f and Uni0515GCr primer set
Summary
Gut microbiota is an essential factor in development of cellular and humoral components of the GALT (Sommer and Bäckhed, 2013), while its dysbiosis have been correlated with various diseases (Carding et al, 2015). More data on the effect of gut microbiota on the inflammatory CNS pathology has been obtained from studies on EAE, an animal model of multiple sclerosis. These data support the idea that the gut microbiota dysbiosis is actively contributing to development and progression of multiple sclerosis (Ochoa-Reparaz et al, 2009; Berer et al, 2011; Lee et al, 2011). Gut microbiota-imposed regulation of anti-CNS immune response is performed through generation of tolerogenic dendritic cells and regulatory T cells. The adjustment of the deviated gut microbiota could be a valuable strategy for the prevention and treatment of multiple sclerosis
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