Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 50, Pages 25311-25321Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1905787116
Keywords
microbiota; remyelination; microglia; macrophage; oligodendrocyte progenitor cell
Categories
Funding
- UK Multiple Sclerosis Society
- The British Trust for the Myelin Project
- MedImmune
- The Adelson Medical Research Foundation
- Wellcome Trust
- Biotechnology and Biological Sciences Research Council (BBSRC)
- Leverhulme Trust
- MRC
- Jean Shanks Foundation
- James Baird Fund
- European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) fellowship
- Britain Israel Research and Academic Exchange Partnership (BIRAX) fellowship
- BBSRC [BB/J01026X/1, BB/N003721/1] Funding Source: UKRI
- MRC [MR/P011705/1, MC_PC_13030, MR/P01836X/1, MC_UP_A090_1006] Funding Source: UKRI
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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.
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