title: Brain microbiota disruption within inflammatory demyelinating lesions in multiple sclerosis.
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/cm3and 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.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton AB Canada.|Department of Laboratory Medicine &Pathology, University of Alberta, Edmonton AB Canada.
authors.forename: W G
authors.initials: WG
authors.lastname: Branton
authors.affiliation: Department of Laboratory Medicine &Pathology, University of Alberta, Edmonton AB Canada.|Department of Psychiatry, University of Alberta, Edmonton AB Canada.
authors.forename: J Q
authors.initials: JQ
authors.lastname: Lu
authors.affiliation: Department of Medicine, McMaster University, Hamilton ON Canada.
authors.forename: M G
authors.initials: MG
authors.lastname: Surette
authors.affiliation: Genome Sciences Centre, Vancouver BC, Canada.
authors.forename: R A
authors.initials: RA
authors.lastname: Holt
authors.affiliation: Department of Neurosciences, Section of Medical Physiology, Faculty of Medical Sciences, University Medical Center Groningen, University of Groningen, Groningen Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Lind
authors.affiliation: Multiple Sclerosis Centre, University of Alberta, Edmonton AB Canada.
authors.forename: J D
authors.initials: JD
authors.lastname: Laman
authors.affiliation: Department of Medicine, University of Alberta, Edmonton AB Canada.|Department of Laboratory Medicine &Pathology, University of Alberta, Edmonton AB Canada.|Department of Neurosciences, Section of Medical Physiology, Faculty of Medical Sciences, University Medical Center Groningen, University of Groningen, Groningen Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Power
mesh_terms: D039903:Actinobacteria / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D001921:Brain / Q000382:microbiology* / Q000473:pathology; D016022:Case-Control Studies; D000458:Cyanobacteria / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D004269:DNA, Bacterial / Q000235:genetics; D003711:Demyelinating Diseases / Q000382:microbiology* / Q000473:pathology; D064806:Dysbiosis / Q000382:microbiology* / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation; D008297:Male; D064307:Microbiota / Q000235:genetics; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000382:microbiology* / Q000473:pathology; D025341:Principal Component Analysis; D020560:Proteobacteria / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D066127:White Matter / Q000382:microbiology* / Q000473:pathology
chemical_list: D004269:DNA, Bacterial; D012336:RNA, Ribosomal, 16S