Author Of 2 Presentations
P0670 - Ecological and functional alterations of the gut microbiome in different stages of multiple sclerosis (ID 1118)
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).
P0998 - The immunological features of peripheral blood findings from multiple sclerosis patients sustaining NEDA-3. (ID 1546)
Abstract
Background
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. MS patients are treated with disease modifying drug (DMD) to prevent relapse and disease progression. Recently, the concept of NEDA (no evidence of disease activity) is proposed as the end point of efficacious therapy, but the mechanism related to NEDA is not well known.
Objectives
The objective of this reserch is to identify the immunological features that contribute to the sustaining of NEDA-3 in MS patients.
Methods
Peripheral blood from MS patients sustaining NEDA-3 for more than 2 years (n=32) and EDA patients (n=9) were obtained. In NEDA group, the patients treated with interferon (IFN) β, PSL, Glatiramer acetate (GA), natalizumab (NTZ), without DMT were 10, 8, 5, 4, and 5 cases respectively. We defined EDA as patients having relapse more than twice in a year with same medication in this study. We evaluated the frequency of B, T, NK cells and monocytes subsets by flow cytometry. Moreover, we analyzed the correlation between the clinical features and the frequency of monocyte subsets.
Results
The frequency of non-classical monocytes (NCM;CD14dimCD16+monocyte) in peripheral blood was significantly higher in NEDA group (6.6±4.1%(average±SD), p<0.01) than in EDA group (2.6±1.2%). Comparing by drug in NEDA group, the frequency of NCM was higher in patients with IFNβ (9.7±3.7%) than in patients with PSL, GA, NTZ (p<0.01, <0.01, =0.05, respectively). The intermediate monocytes (IM;CD14++CD16+monocyte) showed similar tendency to NCM, but the difference was not statistically significant. The frequency of NCM correlated positively with those of activated Tregs (foxp3high CD4+T cells, p=0.01) in NEDA group. The frequency of NCM also correlated positively with the duration of sustaining NEDA (p<0.05) in NEDA group.
Conclusions
Non-classical monocytes might play an important role in immune tolerance of MS patients sustaining NEDA-3 with IFNβ.