Spectrum of Microbial Sequences and a Bacterial Cell Wall Antigen in Primary Demyelination Brain Specimens Obtained from Living Patients

Abstract

Multiple sclerosis (MS) is an autoimmune disease characterized by multiple lesions in the brain and spinal cord. We used RNA sequencing to identify microbial sequences and characterize human gene expression patterns in 30 human brain biopsy specimens. RNAs which aligned to known microbial taxa, were significantly enriched in 10 of 12 primary demyelination (MS) brain specimens compared to a group of 15 epilepsy controls, leading to a list of 29 MS microbial candidate genera from 11 different phyla. Most of the candidate MS microbes are anaerobic bacteria. While there were some shared candidates, each of the 10 MS samples with significant microbial RNA enrichment had a distinct set microbial candidates. The fraction of microbial sequencing reads was greater for the MS group (128.8 PPM) compared to the controls (77.4 PPM, p = 0.016). Bacterial peptidoglycan was demonstrated in brain tissue sections from several MS subjects. Human gene expression analysis showed increased expression of inflammation-related pathways in the MS group. This data shows that demyelinating brain lesions are associated with the presence of microbial RNA sequences and bacterial antigen. This suggests that MS is triggered by the presence of a diverse set of microbes within a lesion.