Abstract
Objective: To investigate immune cells of the colonic mucosa and fecal short-chain fatty acids (SCFAs) in treatment-naive patients with a clinically isolated syndrome (CIS) or early relapsing MS.
Methods: In this cross-sectional proof-of-concept study, we obtained mucosal specimens during ileocolonoscopy from 15 untreated patients with CIS/MS and 10 controls. Mucosal immune cells were analyzed by FACS, and gas chromatography-mass spectrometry measurements of stool samples served to determine SCFA.
Results: The number of total dendritic cells (DCs), CD103+ tolerogenic DCs, and CD4+25+127–regulatory T cells (Tregs) was significantly reduced in the distal colon of patients with CIS/MS compared with controls, whereas we found no differences in the proximal colon. The patients' fecal samples also showed a substantially lower content of SCFA and especially lower levels of butyrate and acetate.
Conclusions: Our findings indicate a disturbed homeostasis of colonic DCs and Tregs in patients with MS which could be associated with colonic SCFA depletion. Although not implying causality, these findings confirm parallel abnormalities of the gut in MS and warrant further research if modulation of the colonic SCFA profile or the colonic Treg pool can serve to modify the course of MS.
GLOSSARY
- CIS=
- clinically isolated syndrome;
- CNS=
- central nervous system;
- DC=
- dendritic cell;
- EAE=
- experimental autoimmune encephalomyelitis;
- EDSS=
- Expanded Disability Status Scale;
- EI=
- electron impact;
- FCS=
- fetal calf serum;
- FMO=
- fluorescence minus one;
- GC-EI/MS=
- gas chromatography-electron impact-mass spectrometry;
- HBSS=
- Hanks balanced salt solution;
- HPLC=
- high-performance liquid chromatography;
- IQR=
- interquartile range;
- IRB=
- institutional review board;
- LPDC=
- lamina propria DC;
- PEG=
- polyethylene glycol;
- RPMI=
- Roswell Park Memorial Institute;
- SCFA=
- short-chain fatty acid;
- Tregs=
- regulatory T cell
Footnotes
↵* These authors contributed equally to this work.
Funding information and disclosures are provided at the end of the article. Go to Neurology.org/nn for full disclosure forms. The Article Processing Charge was funded by the authors.
Supplemental data at Neurology.org/nn
- Received January 3, 2017.
- Accepted in final form April 13, 2017.
- Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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