Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published October 3, 2017 | Supplemental Material + Erratum + Published
Journal Article Open

Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models


The gut microbiota regulates T cell functions throughout the body. We hypothesized that intestinal bacteria impact the pathogenesis of multiple sclerosis (MS), an autoimmune disorder of the CNS and thus analyzed the microbiomes of 71 MS patients not undergoing treatment and 71 healthy controls. Although no major shifts in microbial community structure were found, we identified specific bacterial taxa that were significantly associated with MS. Akkermansia muciniphila and Acinetobacter calcoaceticus, both increased in MS patients, induced proinflammatory responses in human peripheral blood mononuclear cells and in monocolonized mice. In contrast, Parabacteroides distasonis, which was reduced in MS patients, stimulated antiinflammatory IL-10–expressing human CD4+CD25+ T cells and IL-10+FoxP3+ Tregs in mice. Finally, microbiota transplants from MS patients into germ-free mice resulted in more severe symptoms of experimental autoimmune encephalomyelitis and reduced proportions of IL-10+ Tregs compared with mice "humanized" with microbiota from healthy controls. This study identifies specific human gut bacteria that regulate adaptive autoimmune responses, suggesting therapeutic targeting of the microbiota as a treatment for MS.

Additional Information

© 2017 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). https://creativecommons.org/licenses/by-nc-nd/4.0/ Edited by Lawrence Steinman, Stanford University School of Medicine, Stanford, CA, and approved August 7, 2017 (received for review June 30, 2017) Published online before print September 11, 2017, doi: 10.1073/pnas.1711235114 We thank the patients who participated in this study and M. Fischbach, S. S. Zamvil, and J. R. Oksenberg for critically reading the manuscript. We also thank the international multiple sclerosis microbiome consortium (iMSMS) for helpful discussions and feedback. This work was supported by the US National Multiple Sclerosis Society, a NIH Institutional Research and Academic Career Development Award Postdoctoral Fellowship, the US Department of Defense, the Valhalla Charitable Foundation, the Emerald Foundation, and Heritage Medical Research Institute. E.C. and B.B.Y. contributed equally to this work. Author contributions: E.C., S.L.H., I.K.S., P.C., B.A.C.C., R. Knight, S.K.M., and S.E.B. designed research; E.C., B.B.Y., T.F.R., S.S., C.A.N., R. Kanner, Y.B., Y.K.L., E.C.-H., I.K.S., M.G., P.C., B.A.C.C., R. Knight, and S.K.M. performed research; R. Knight and S.K.M. contributed new reagents/analytic tools; E.C., B.B.Y., J.W.D., C.A.N., M.G., Y.Z., S.K.M., and S.E.B. analyzed data; and E.C. and S.E.B. wrote the paper. The authors declare no conflict of interest. This article is a PNAS Direct Submission. Data deposition: Normalized datasets related to this paper are available from the UCSF Data Sharing Service (Dash) at https://doi.org/10.7272/Q6N58JH2 and https://doi.org/10.7272/Q6RX997G. Raw data are available upon request. This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1711235114/-/DCSupplemental.


The authors note that the author name Yungjiao Zhu should instead appear as Yunjiao Zhu. The corrected author line appears below. The online version has been corrected.

Attached Files

Published - PNAS-2017-Cekanaviciute-10713-8.pdf

Supplemental Material - pnas.1711235114.sapp.pdf

Erratum - E8943.full.pdf


Files (5.8 MB)
Name Size Download all
34.5 kB Preview Download
1.4 MB Preview Download
4.4 MB Preview Download

Additional details

August 21, 2023
October 23, 2023