Gut Microbiota Interventions With Clostridium butyricum and Norfloxacin Modulate Immune Response in Experimental Autoimmune Encephalomyelitis Mice.

Hao Chen,Lei Si,Yingying Liu,Xiaohong Chen,Xueying Ma,Lili Ma,Xiuli Lin,Xiaomeng Ma,Zhaoyu Chen

doi:10.3389/fimmu.2019.01662

Abstract

Gut microbiota has been proposed as an important environmental factor which can intervene and modulate central nervous system autoimmunity. Here, we altered the composition of gut flora with Clostridium butyricum and norfloxacin in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. We found that appropriate C. butyricum (5.0 × 106 CFU/mL intragastrically daily, staring at weaning period of age) and norfloxacin (5 mg/kg intragastrically daily, 1 week prior to EAE induction) treatment could both ameliorate EAE although there are obvious differences in gut microbiota composition between these two interventions. C. butyricum increased while norfloxacin decreased the abundance and diversity of the gut microbiota in EAE mice, and both of the treatments decreased firmicutes/bacteroidetes ratio. In the genus level, C. butyricum treatment increased the abundance of Prevotella while Akkermansia and Allobaculum increased in norfloxacin treatment. Moreover, both interventions reduced Desulfovibroneceae and Ruminococcus species. Although there was discrepancy in the gut microbiota composition with the two interventions, C. butyricum and norfloxacin treatment both reduced Th17 response and increased Treg response in the gastrointestinal tract and extra-gastrointestinal organ systems in EAE mice. And the reduced activity of p38 mitogen-activated kinase and c-Jun N-terminal kinase signaling in spinal cord could be observed in the two interventions. The results suggested that manipulation of gut microbiota interventions should take factors such as timing, duration, and dosage into consideration. The discrepancy in the gut microbiota composition and the similar protective T cells response of C. butyricum and norfloxacin implies that achieving intestinal microecology balance by promoting and/or inhibiting the gut microbiota contribute to the well-being of immune response in EAE mice.

Highlights

Multiple sclerosis (MS) is a chronic autoimmune inflammatory demyelinating disease of the central nervous system (CNS) and its incidence continues to increase worldwide [1]
As for neuropathology, both treatments could decrease lymphocyte infiltration and plaques of demyelination in lumber spinal cord (Figures 1B–E). These results indicated that gut microbiota interventions with C. butyricum and norfloxacin both could ameliorate clinical severity and neuropathology of EAE mice
Bacterial community has been proposed as an important environmental factor which can intervene and modulate CNS autoimmunity

Summary

Introduction

Multiple sclerosis (MS) is a chronic autoimmune inflammatory demyelinating disease of the central nervous system (CNS) and its incidence continues to increase worldwide [1]. The pathogenesis of MS is complex and therapeutic effects are not satisfying. Environmental factors play an important role in pathogenesis of MS. Gut microbiota can make a major contribution to the disease both in susceptibility and protection [2,3,4]. The discovery of MS-related pathogenic and/or protective gut microbiota organisms or their products would provide novel opportunities for diagnosis and therapy of the disease. The latter would mainly rely on appropriate probiotic and/or antibiotic treatments, dietary modification, and fecal microbial transplantation

Methods

Results

Conclusion