The microbiota regulates murine inflammatory responses to toxin-induced CNS demyelination but has minimal impact on remyelination

Christopher E McMurran, Alerie Guzman de la Fuente, Rosana Penalva, Ofra Ben Menachem-Zidon, Yvonne Dombrowski, John Falconer, Ginez A Gonzalez, Chao Zhao, Fynn N Krause, Adam M H Young, Julian L Griffin, Clare A Jones, Claire Hollins, Markus M Heimesaat, Denise C Fitzgerald, Robin J M Franklin

Research output: Contribution to journalArticle

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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.

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Early online date18 Nov 2019
DOIs
Publication statusEarly online date - 18 Nov 2019

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Microbiota
Demyelinating Diseases
Central Nervous System
Oligodendroglia
Anti-Bacterial Agents
Regeneration
Stem Cells
Probiotics
Myelin Sheath
Multiple Sclerosis
Cell Differentiation
Therapeutics

Bibliographical note

Copyright © 2019 the Author(s). Published by PNAS.

Cite this

McMurran, Christopher E ; Guzman de la Fuente, Alerie ; Penalva, Rosana ; Ben Menachem-Zidon, Ofra ; Dombrowski, Yvonne ; Falconer, John ; Gonzalez, Ginez A ; Zhao, Chao ; Krause, Fynn N ; Young, Adam M H ; Griffin, Julian L ; Jones, Clare A ; Hollins, Claire ; Heimesaat, Markus M ; Fitzgerald, Denise C ; Franklin, Robin J M. / The microbiota regulates murine inflammatory responses to toxin-induced CNS demyelination but has minimal impact on remyelination. In: Proceedings of the National Academy of Sciences of the United States of America. 2019.
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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.",
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The microbiota regulates murine inflammatory responses to toxin-induced CNS demyelination but has minimal impact on remyelination. / McMurran, Christopher E; Guzman de la Fuente, Alerie; Penalva, Rosana; Ben Menachem-Zidon, Ofra; Dombrowski, Yvonne; Falconer, John; Gonzalez, Ginez A; Zhao, Chao; Krause, Fynn N; Young, Adam M H; Griffin, Julian L; Jones, Clare A; Hollins, Claire; Heimesaat, Markus M; Fitzgerald, Denise C; Franklin, Robin J M.

In: Proceedings of the National Academy of Sciences of the United States of America, 18.11.2019.

Research output: Contribution to journalArticle

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AU - McMurran, Christopher E

AU - Guzman de la Fuente, Alerie

AU - Penalva, Rosana

AU - Ben Menachem-Zidon, Ofra

AU - Dombrowski, Yvonne

AU - Falconer, John

AU - Gonzalez, Ginez A

AU - Zhao, Chao

AU - Krause, Fynn N

AU - Young, Adam M H

AU - Griffin, Julian L

AU - Jones, Clare A

AU - Hollins, Claire

AU - Heimesaat, Markus M

AU - Fitzgerald, Denise C

AU - Franklin, Robin J M

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