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Mucosal biopsy shows immunologic changes of the colon in patients with early MS
Adrian Mathias Moser1, Walter Spindelboeck1, Heimo Strohmaier1
1Department of Internal Medicine (A.M.M., W.S., C.H.), Division of Gastroenterology and Hepatology, Theodor Escherich Laboratory for Microbiome Research (A.M.M., W.S., G.G., P.W., C.H.), Center for Medical Research (H.S.), Department of Neurology (C.E., T.G., S.F., F.F., M.K.), and Institute of Pathology (G.G., P.W.), Medical University of Graz, Austria.
Insights
Patients with early multiple sclerosis (MS) show reduced colonic immune cells and short-chain fatty acids (SCFAs). These gut abnormalities in MS may impact disease course and warrant further investigation.
Area of Science:
- Neuroimmunology
- Gastroenterology
- Microbiome Research
Background:
- Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
- The gut microbiome and its metabolites, such as short-chain fatty acids (SCFAs), are increasingly recognized for their role in immune regulation.
- Alterations in gut immunity and microbial metabolites may contribute to the pathogenesis of MS.
Purpose of the Study:
- To investigate the characteristics of colonic immune cells and fecal SCFA levels in treatment-naive patients with clinically isolated syndrome (CIS) or early relapsing-remitting MS.
- To explore potential associations between colonic immune cell populations and SCFA profiles in these patients.
Main Methods:
- Cross-sectional, proof-of-concept study involving 15 untreated patients with CIS/MS and 10 healthy controls.
- Ileocolonoscopy was performed to obtain colonic mucosal specimens for flow cytometry analysis of immune cells (dendritic cells [DCs], regulatory T cells [Tregs]).
- Fecal samples were analyzed using gas chromatography-mass spectrometry to quantify SCFA levels (butyrate, acetate, etc.).
Main Results:
- A significant reduction in total DCs, CD103+ tolerogenic DCs, and CD4+25+127- regulatory T cells (Tregs) was observed in the distal colon of CIS/MS patients compared to controls.
- No significant differences in these immune cells were found in the proximal colon.
- Patients with CIS/MS exhibited substantially lower fecal SCFA content, particularly reduced levels of butyrate and acetate.
Conclusions:
- The findings suggest a disturbed homeostasis of colonic dendritic cells and regulatory T cells in early MS, potentially linked to SCFA depletion in the gut.
- These results highlight parallel abnormalities in the gut of MS patients, although causality is not implied.
- Further research is warranted to determine if modulating the colonic SCFA profile or Treg pool could influence the course of MS.
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.
