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Neurol Neuroimmunol Neuroinflamm. 2018 Oct 26;6(1):e517. doi: 10.1212/NXI.0000000000000517. eCollection 2019 Jan.

Disease-modifying therapies alter gut microbial composition in MS.

Author information

1
Department of Neurology (I.K.S., A.N., R.B., Y.B.), Department of Neuroscience (Y.Z., P.C.), and Department of Genetics & Genomic Sciences, Icahn Institute for Genomics & Multiscale Biology (J.C.C.), Icahn School of Medicine at Mount Sinai; Department of Neurology (E.C., E.C.-H., S.S., B.A.C.C., S.E.B.), Weill Institute for Neurosciences, University of California, San Francisco; E.C. is now with Universities Space Research Association, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA; Department of Pediatrics (J.D., R.K.), Department of Computer Science & Engineering (R.K.), and Center for Microbiome Innovation (R.K.), University of California, San Diego; and Neuroscience Initiative (P.C.), Advanced Research Science Center at the Graduate Center of the City University of New York.

Abstract

Objective:

To determine the effects of the disease-modifying therapies, glatiramer acetate (GA) and dimethyl fumarate (DMF), on the gut microbiota in patients with MS.

Methods:

Participants with relapsing MS who were either treatment-naive or treated with GA or DMF were recruited. Peripheral blood mononuclear cells were immunophenotyped. Bacterial DNA was extracted from stool, and amplicons targeting the V4 region of the bacterial/archaeal 16S rRNA gene were sequenced (Illumina MiSeq). Raw reads were clustered into Operational Taxonomic Units using the GreenGenes database. Differential abundance analysis was performed using linear discriminant analysis effect size. Phylogenetic investigation of communities by reconstruction of unobserved states was used to investigate changes to functional pathways resulting from differential taxon abundance.

Results:

One hundred sixty-eight participants were included (treatment-naive n = 75, DMF n = 33, and GA n = 60). Disease-modifying therapies were associated with changes in the fecal microbiota composition. Both therapies were associated with decreased relative abundance of the Lachnospiraceae and Veillonellaceae families. In addition, DMF was associated with decreased relative abundance of the phyla Firmicutes and Fusobacteria and the order Clostridiales and an increase in the phylum Bacteroidetes. Despite the different changes in bacterial taxa, there was an overlap between functional pathways affected by both therapies.

Interpretation:

Administration of GA or DMF is associated with differences in gut microbial composition in patients with MS. Because those changes affect critical metabolic pathways, we hypothesize that our findings may highlight mechanisms of pathophysiology and potential therapeutic intervention requiring further investigation.

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