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Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination
Published on: September 12, 2016
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Brain microbiota disruption within inflammatory demyelinating lesions in multiple sclerosis.
W G Branton1,2, J Q Lu2,3, M G Surette4
1Department of Medicine, University of Alberta, Edmonton AB Canada.
Scientific Reports
|November 29, 2016
Summary
Multiple sclerosis (MS) brains show an altered gut microbiome composition, specifically an increase in Proteobacteria. This dysbiosis correlates with inflammatory demyelination, suggesting a role in MS pathogenesis.
Area of Science:
- Neuroscience
- Microbiology
- Immunology
Background:
- Microbial communities are present in healthy tissues but can be disrupted during disease.
- Bacterial components have been detected in brains across various species, even without neurological conditions.
Purpose of the Study:
- To investigate the composition and abundance of microbiota in the brains of multiple sclerosis (MS) patients compared to non-MS controls.
- To explore the relationship between brain microbiota, demyelination, and neuroinflammation in MS.
Main Methods:
- Analysis of frozen and fixed autopsied brain samples using neuropathological, molecular, and bioinformatics tools.
- 16S rRNA sequencing and RNA sequencing (RNAseq) to identify bacterial composition and gene expression.
- Immunohistochemistry to detect bacterial components like peptidoglycan (PGN).
Main Results:
- Proteobacteria were the dominant phylum with reduced diversity in the cerebral white matter (WM) of MS patients compared to controls.
- Both groups had similar bacterial genome counts (1,200-1,400/cm³), but MS brains showed a predominance of Proteobacteria linked to increased inflammatory gene expression.
- PGN immunodetection correlated significantly with demyelination and neuroinflammation in MS brains, with these factors explaining 86% of the variance.
Conclusions:
- Multiple sclerosis is associated with an organ-specific dysbiosis, characterized by an altered brain microbial composition.
- The findings suggest a link between inflammatory demyelination and microbial dysbiosis in the pathogenesis of MS.
- Bacterial components, particularly PGN, may play a role in driving neuroinflammation and demyelination in MS.
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