The microbiota regulates murine inflammatory responses to toxin-induced CNS demyelination but has minimal impact on remyelination
File(s)
Published version
Author(s)
McMurran, Christopher E
Guzman de la Fuente, Alerie
Penalva, Rosana
Ben Menachem-Zidon, Ofra
Dombrowski, Yvonne
Type
Journal Article
Abstract
The microbiota is now recognized as a key influence on the host immune response in the central nervous system (CNS). As such, there has been some progress toward therapies that modulate the microbiota with the aim of limiting immune-mediated demyelination, as occurs in multiple sclerosis. However, remyelination—the regeneration of myelin sheaths—also depends upon an immune response, and the effects that such interventions might have on remyelination have not yet been explored. Here, we show that the inflammatory response during CNS remyelination in mice is modulated by antibiotic or probiotic treatment, as well as in germ-free mice. We also explore the effect of these changes on oligodendrocyte progenitor cell differentiation, which is inhibited by antibiotics but unaffected by our other interventions. These results reveal that high combined doses of oral antibiotics impair oligodendrocyte progenitor cell responses during remyelination and further our understanding of how mammalian regeneration relates to the microbiota.
Date Issued
2019-11-18
Date Acceptance
2019-11-01
Citation
Proceedings of the National Academy of Sciences, 2019, 116 (50), pp.25311-25321
ISSN
0027-8424
Publisher
Proceedings of the National Academy of Sciences
Start Page
25311
End Page
25321
Journal / Book Title
Proceedings of the National Academy of Sciences
Volume
116
Issue
50
Copyright Statement
© 2019 the Author(s). Published by PNAS.
This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/).
This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/).
Sponsor
Medical Research Council
Identifier
https://www.pnas.org/content/early/2019/11/15/1905787116
Grant Number
MR/P011705/1
Subjects
macrophage
microbiota
microglia
oligodendrocyte progenitor cell
remyelination
Publication Status
Published
Date Publish Online
2019-12-10