LAUSR

Significance People with multiple sclerosis have a microbiota distinct from healthy controls, and there is growing interest in how these differences might contribute to the onset and progression of CNS autoimmunity. However, the impact that the microbiota may also have on the endogenous regeneration of myelin—remyelination—has not yet been explored. Here we show that inflammatory responses during remyelination depend upon the microbiota, being modulated by antibiotics or probiotics or in germ-free mice. In contrast, these interventions had minimal impact on the activity of oligodendrocyte progenitor cells, with only supratherapeutic doses of antibiotics having an inhibitory effect. Our results suggest that endogenous CNS remyelination is largely resilient to interventions that modify the microbiota. 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.