Mechanism of gut microbiota and Axl/SOCS3 in experimental autoimmune encephalomyelitis.

Xiao-Ling Li,Meng-Jiao Sun,Qin-Fang Xie,Man-Xia Wang,Cai-Cai Bao,Bo-Yao Yuan,Bo Zhang,Li-Juan Wang

doi:10.1042/bsr20190228

Abstract

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS). The present study explored the role of intestinal microbiota in the initiation and propagation of mice induced by experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. 48 C57BL/6 were randomly divided into control group and EAE group. The changes of body weight and the scores of neurological function were recorded. The mRNA expression of the receptor tyrosine kinase subfamily (AXL) was detected by real-time quantitative PCR. The levels of IL-17 and IFN-γ in blood samples were examined by ELISA. The intestinal microbial composition of mice at different time points during the EAE induction was analyzed by 16S rRNA gene-based sequencing. In EAE group, the body weight began to reduce at day 3 and neurological symptoms began to appear at day 7 after EAE induction. The levels of IL-17 and IFN-γ in EAE group reached the peak at day 21 and then decreased gradually. However, the expression of Axl and SOCS3 reached the lowest level at day 21 and then increased gradually. The microbiome analyses revealed that the abundances of Alistipes, Blautia, and Lachnospiraceae_NK4A136_group were significantly changed at day 14, whereas the abundances of Allobaculum, Eubacterium and Helicobacter were significantly changed at day 30 of EAE induction. The prevotellaceae_NK3B31_group may be key bacteria that contribute to the development of MS. Regulation of intestinal microbiota composition can become a new therapeutic target for the treatment of MS.

Highlights

Multiple sclerosis (MS) is a devastating autoimmune disease leading to progressive deterioration of the central nervous system (CNS) [1]
In EAE group, the body weight began to reduce at day 3 and neurological symptoms began to appear at day 7 after EAE induction
The microbiome analyses revealed that the abundances of Alistipes, Blautia, and Lachnospiraceae NK4A136 group were significantly changed at day 14, whereas the abundances of Allobaculum, Eubacterium and Helicobacter were significantly changed at day 30 of EAE induction

Summary

Introduction

Multiple sclerosis (MS) is a devastating autoimmune disease leading to progressive deterioration of the central nervous system (CNS) [1]. The incidence of MS in women is higher than that in men and it is the most important nervous system disease causing nervous dysfunction in young adults [3,4]. The mammalian intestine is colonized by a complex microbial community, which consists of numerous microorganisms such as viruses, fungi, and bacteria [8]. Diverse bacteria in the intestine provide rich sources of microbial-derived antigen that can drive and promote the development of host immune system [10]. Accumulating evidences have showed that the gut microbiota is another important environmental factor that is associated with the development of MS [11,12,13]. Relapsing-remitting mice can spontaneously develop experimental autoimmune encephalomyelitis (EAE), a murine disease model that

Methods

Results

Conclusion