A novel probiotic strain exerts therapeutic effects on mouse model of multiple sclerosis by altering the expression of inflammasome and IDO genes and modulation of T helper cytokine profile.

Saba Sadeghirashed,Javad Arasteh,Fatemeh Kazemi,Maryam Tajabadi Ebrahimi,Saba Taheri

doi:10.1007/s11011-021-00857-7

Abstract

Multiple sclerosis is an inflammatory demyelinating disease that commences to neuronal cell destruction. Recently, a promising evidence of synergic effects of combined supplementation with vitamin D and probiotics in modulating the gut microbiota and metabolome is emerging. Bacillus Coagulans IBRC-M10791 as a novel strain was chosen, prevention and treatment impacts of regular administered were studied in Cuprizone-induced C57bl/6 mouse of demyelination. The mice were divided into six groups and received a daily dose of cuprizone or probiotics. To investigate the effect of probiotic, the IDO-1, CYP27B1, NLRP1, NLRP3, and AIM2 expression were estimated by Real-Time PCR, and IL-4, IL-17, IFN-gamma, and TGF-beta cytokines were measured by ELISA. The results showed that there was significant decrease in IL-17 and IFN-γ and modulatory effects on IL-4 and TGF-β. On the other hand, we demonstrated that there are significant decrease for expression of IDO-1, CYP27b1, NLRP1, NLRP3 and AIM2 genes in prevention and treatment groups compared to cuprizone group. Also, a significant enhancement in rate of remyelination and alternations proved by LFB staining and Y-Maze test. In conclusion, our study provides insight into how the therapeutic effect of the chosen strain of probiotic was correlated with the modulation of the level of inflammatory and anti-inflammatory cytokines. Further, we demonstrated that the expression of genes related to Tryptophan, Vitamin D and Inflammasome pathways could be affected by B.coagulans. Our study could be beneficial to provide a novel Co-therapeutic strategy for Multiple sclerosis.

Highlights

Multiple sclerosis is an autoimmune, inflammatory disease, and one of the most common diseases of the central nervous system that most often occurs in the age range of 20 to 40 years(Schattling et al 2014)
We showed that Bacillus coagulans decreased the IFN-g level, which was consistent with previous studies
In this research we found that Bacillus coagulans decreased the IL-17 level, which is similar to other studies

Summary

Introduction

Multiple sclerosis is an autoimmune, inflammatory disease, and one of the most common diseases of the central nervous system that most often occurs in the age range of 20 to 40 years(Schattling et al 2014). Various studies on patients with MS indicate that multiple aspects of the innate and adaptive immune systems do not operate correctly in these patients(Høglund and Maghazachi 2014). Excessive increase in invasive activity of Th1 and Th17 by secreting the pro-inflammatory cytokines IFN-γ and IL-17, respectively, plays a crucial role in the immunopathogenesis of MS as well as modulation of anti-inflammatory cytokines such as IL-4 and TGF-β through Th2 and Treg cells(Duhen et al 2013). IFN-γ expression increases transcription of the IDO gene, resulting in decreased T cell activation and proliferation through tryptophan depletion and production of Treg lymphocytes(Lee and Mazmanian 2010). Researches have shown that this gene is involved in the pathogenesis of autoimmune diseases, and a change in its expression could indicate the onset of relapse in MS patients(Lovelace et al 2016). Inflammasome complex as part of this system detect inflammatory signals generated by infection or endogenous and with increasing the expression of genes such as NLRP1, NLRP3, and AIM2

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