Brain microbiota disruption within inflammatory demyelinating lesions in multiple sclerosis.

W G Branton,C Power,R A Holt,J Q Lu,J D Laman,M G Surette,J Lind

doi:10.1038/srep37344

Abstract

Microbial communities reside in healthy tissues but are often disrupted during disease. Bacterial genomes and proteins are detected in brains from humans, nonhuman primates, rodents and other species in the absence of neurological disease. We investigated the composition and abundance of microbiota in frozen and fixed autopsied brain samples from patients with multiple sclerosis (MS) and age- and sex-matched nonMS patients as controls, using neuropathological, molecular and bioinformatics tools. 16s rRNA sequencing revealed Proteobacteria to be the dominant phylum with restricted diversity in cerebral white matter (WM) from MS compared to nonMS patients. Both clinical groups displayed 1,200–1,400 bacterial genomes/cm3 and low bacterial rRNA:rDNA ratios in WM. RNAseq analyses showed a predominance of Proteobacteria in progressive MS patients’ WM, associated with increased inflammatory gene expression, relative to a broader range of bacterial phyla in relapsing-remitting MS patients’ WM. Although bacterial peptidoglycan (PGN) and RNA polymerase beta subunit immunoreactivities were observed in all patients, PGN immunodetection was correlated with demyelination and neuroinflammation in MS brains. Principal component analysis revealed that demyelination, PGN and inflammatory gene expression accounted for 86% of the observed variance. Thus, inflammatory demyelination is linked to an organ-specific dysbiosis in MS that could contribute to underlying disease mechanisms.

Highlights

Bacterial rRNA sequence analyses of cloned amplicons derived from nonMS white matter displayed greater molecular diversity within multiple clones per sample compared to MS white matter (p < 0.01) (Fig. 1C)
The current study shows the presence of bacterial RNA and DNA sequences and proteins in human brain which are disrupted in conjunction with inflammatory demyelination in patients with MS
Proteobacteria represented the chief bacterial phylum detected in human brain with restricted molecular diversity in MS brains despite the increased density of bacterial glycoproteins within demyelinating lesions

Summary

Introduction

Correspondence and requests for materials should be addressed to C.P. N/A p value Non Significant Non Significant bacterial proteins, in brains from humans (in the presence or absence of neurological disease), nonhuman primates[23], rodents[24] and other species[25]. We examined bacterial quantity and genetic diversity in brains from patients with MS and other diseases. Bacterial abundance and molecular diversity were associated with both neuropathology and proinflammatory gene expression in patients with MS, revealing disturbances in human brain microbiota in a disease context

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Results

Conclusion