National Institute of Neuroscience, National Center of Neurology and Psychiatry

Author Of 1 Presentation

Microbiome Poster Presentation

P0677 - Possible association between miRNAs and gut microbiota in pathogenesis of Multiple sclerosis (ID 1624)

Speakers
Presentation Number
P0677
Presentation Topic
Microbiome

Abstract

Background

Multiple Sclerosis (MS) is an autoimmune demyelinating disease of CNS, involving interplay of multiple genetic and environmental factors, which leads to a chronic activation of the immune cells targeting CNS autoantigen. Involvement of microbiota has been correlated with the pathogenesis of MS, further mechanistic analyses are needed. Circulating extracellular vesicles(EVs) including exosomes play an important role in many signaling pathway by regulating gene expression, and the role of exosomal microRNA in MS has been demonstrated in our previous study (Kimura et al. Nature Comm 2018). Here we explored if extracellular vesicles including exosomes can be a communication tool between gut microbiota and the host immune system.

Objectives

Role of gut microbiome in generation of circulating exosomes and miRNAs.

Elucidate the relationship between circulating miRNA and gut microbiota in the pathogenesis of MS, using EAE model.

Methods

We generated gut microbiome dysbiosis model mice by oral administration of non-absorbing antibiotics cocktail (ABX) containing kanamycin, vancomycin and colistin. The model mice were subjected to Experimental autoimmune encephalomyelitis (EAE) by injecting MOG35-55 peptide in CFA. Exosome concentrations in the sera were quantified using enzymatic analysis. MOG tetramer35-55 reactive CD4+ T cells (%) were evaluated for lymphocytes isolated from the CNS, spleen and blood. For cell-free miRNA analysis, total RNA was isolated from the plasma by a Plasma/Serum. Circulating and exosomal RNA Purification kit and miRNA expression analysis was performed by a DNA chip of mouse miRNAs and TaqMan miRNA assay.

Results

Dysbiosis of gut microbiome was shown to ameliorate signs of EAE, along with a notable reduction in the migration of total T cells and MOG tetramer35-55 reactive CD4+ T cells to the CNS. We also revealed substantial changes in the circulating exosome and significant decreases in the expression of exosomal miRNAs, including miR-21a-5p, miR-146-5p, and miR-223-3p. Notably, these miRNAs can directly bind to the 3` UTR region of major genes that controls the T cell migration to the CNS in EAE. The results indicate that gut microbiome would significantly influence the T cell trafficking through exosomal miRNAs in EAE.

Conclusions

Our data support that exosomes and exosomal miRNAs could be the major source of communication between gut microbiome and host immune response.

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