Juntendo University
Immunology

Author Of 1 Presentation

Microbiome Poster Presentation

P0670 - Ecological and functional alterations of the gut microbiome in different stages of multiple sclerosis (ID 1118)

Speakers
Presentation Number
P0670
Presentation Topic
Microbiome

Abstract

Background

Multiple sclerosis (MS), an autoimmune disease of the central nervous system, generally starts as relapsing remitting form (RRMS), but often shifts into secondary progressive MS (SPMS). SPMS represents a more advanced stage of MS, characterized by accumulating disabilities and refractoriness to medications.

Objectives

The aim of this study was to clarify the microbial and functional differences in gut microbiomes of the different stages of MS.

Methods

Here, we compared gut microbiomes of patients with RRMS (n = 62), SPMS (n = 15), and two closely related disorders; atypical MS (n = 21) and neuromyelitis optica spectrum disorder (n = 20) with healthy controls (HC; n = 55) by 16S rRNA gene and whole metagenomic sequencing data from fecal samples and by fecal metabolites.

Results

Each patient group had a number of species having significant changes in abundance in comparison with HC, including short chain fatty acid (SCFA) producing bacteria reduced in MS. Changes in some species had close association with clinical severity of the patients. A marked reduction in butyrate and propionate biosynthesis and corresponding metabolic changes were confirmed in RRMS compared with HC (p = 0.0007 and p = 0.003, respectively). Although bacterial composition analysis showed limited differences between the patient groups, metagenomic functional data disclosed an increase in microbial genes involved in DNA mismatch repair in SPMS as compared to RRMS. Together with an increased ratio of cysteine persulfide to cysteine in SPMS revealed by sulfur metabolomics (p = 0.0152), we postulate that excessive DNA oxidation could take place in the gut of SPMS.

Conclusions

Thus, gut ecological and functional microenvironments were significantly altered in the different stages of MS. In particular, reduced SCFA biosynthesis in RRMS and elevated oxidative level in SPMS were characteristic (Takewaki et al., PNAS. under review).

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