Correlation of Gut Microbiota Composition with Resistance to Experimental Autoimmune Encephalomyelitis in Rats

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.

Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota

“…Unclassified Lactobacillaceae and Bacteroidetes were negatively associated with leptin level, while serum leptin levels were positively correlated with the abundance of Rikenellaceae and Lachnospiraceae (Figure 3E). Probiotic strains, such as Lactobacillus species, have been shown to lessen EAE severity (Stanisavljevic et al, 2016). Although not all the bacteria can be classified to the species level using 16S rRNA gene sequencing, the hypervariable regions of 16S gene allow distinction of different species in Lactobacillaceae (Ravel et al, 2011).…”

“…Of particular interest was the IF-induced enrichment in Lactobacilli , which are commonly used in probiotics because of their positive effects including reduction of inflammatory immune responses (Umbrello and Esposito, 2016). Oral administration of Lactobacilli with myelin antigens has been shown to induce tolerance in the EAE model (Maassen et al, 2003) and enrichment of gut microbiota with Lactobacilli has been associated with resistance to EAE (Stanisavljevic et al, 2016). In the present studies, Lactobacillus species that were over-represented in the setting of IF included L. Johnsonii and L. reuteri, which are well-known to have immunomodulatory properties (Delcenserie et al, 2008; Owaga et al, 2015).…”

Estrogen protection against EAE modulates the microbiota and mucosal-associated regulatory cells

“…We demonstrated that E2 treatment significantly increases the abundance of Lactobacillaceae. This family was associated with induction of regulatory cells and was also shown to be affected by estrogen (Shen et al, 2016, Stanisavljevic et al, 2016). It was reported that different strains of lactobacilli might attenuate EAE by inducing IL-10 producing cells (Lavasani, Dzhambazov, 2010).…”

Gut microbiota and probiotics: novel immune system modulators in myasthenia gravis?

“…On the contrary, in the same animals, PP cells produced higher IL‐10 levels before the immunization and lower levels on day 6. Thus, it has been suggested that IL‐10–producing cells migrate from PPs to MLNs after EAE induction . Recent studies reported increased Firmicutes/Bacteroidetes ratio, increased relative abundance of Streptococcus mitis and S. oralis , and decreased Prevotella with anti‐inflammatory abilities in disease‐active MS patients compared with healthy controls and MS patients with no disease activity.…”