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

By Christopher E McMurran, Alerie Guzman de la Fuente, Rosana Penalva, Ofra Ben Menachem-Zidon, Yvonne Dombrowski, 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 JM Franklin

Posted 13 Mar 2019
bioRxiv DOI: 10.1101/575829

The microbiota is now recognised as a key influence on the host immune response in the central nervous system (CNS). As such, there has been some progress towards 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 negatively influence remyelination and further our understanding of how mammalian regeneration relates to the microbiota.

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