RT Journal Article
SR Electronic
T1 Disease-modifying therapies alter gut microbial composition in MS
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e517
DO 10.1212/NXI.0000000000000517
VO 6
IS 1
A1 Katz Sand, Ilana
A1 Zhu, Yunjiao
A1 Ntranos, Achilles
A1 Clemente, Jose C.
A1 Cekanaviciute, Egle
A1 Brandstadter, Rachel
A1 Crabtree-Hartman, Elizabeth
A1 Singh, Sneha
A1 Bencosme, Yadira
A1 Debelius, Justine
A1 Knight, Rob
A1 Cree, Bruce A.C.
A1 Baranzini, Sergio E.
A1 Casaccia, Patrizia
YR 2019
UL http://nn.neurology.org/content/6/1/e517.abstract
AB 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.DMF=dimethyl fumarate; DMT=disease-modifying therapy; EAE=experimental allergic encephalomyelitis; FDA=Food and Drug Administration; GA=glatiramer acetate; IFN=interferon; LEfSe=linear discriminant analysis effect size; LDA=linear discriminant analysis; OTU=operational taxonomic unit; PICRUSt=phylogenetic investigation of communities by reconstruction of unobserved states