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Butyrate suppresses demyelination and enhances remyelination
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Journal Article
Butyrate suppresses demyelination and enhances remyelination
2019
Overview
Background
The association of gut microbiota and diseases of the central nervous system (CNS), including multiple sclerosis (MS), has attracted much attention. Although a previous analysis of MS gut microbiota revealed a reduction in species producing short-chain fatty acids (SCFAs), the influence of these metabolites on demyelination and remyelination, the critical factors of MS pathogenesis, remains unclear.
Methods
To investigate the relationship between demyelination and gut microbiota, we administered a mixture of non-absorbing antibiotics or SCFAs to mice with cuprizone-induced demyelination and evaluated demyelination and the accumulation of microglia. To analyze the direct effect of SCFAs on demyelination or remyelination, we induced demyelination in an organotypic cerebellar slice culture using lysolecithin and analyzed the demyelination and maturation of oligodendrocyte precursor cells with or without SCFA treatment.
Results
The oral administration of antibiotics significantly enhanced cuprizone-induced demyelination. The oral administration of butyrate significantly ameliorated demyelination, even though the accumulation of microglia into demyelinated lesions was not affected. Furthermore, we showed that butyrate treatment significantly suppressed lysolecithin-induced demyelination and enhanced remyelination in an organotypic slice culture in the presence or absence of microglia, suggesting that butyrate may affect oligodendrocytes directly. Butyrate treatment facilitated the differentiation of immature oligodendrocytes.
Conclusions
We revealed that treatment with butyrate suppressed demyelination and enhanced remyelination in an organotypic slice culture in association with facilitating oligodendrocyte differentiation. Our findings shed light on a novel mechanism of interaction between the metabolites of gut microbiota and the CNS and may provide a strategy to control demyelination and remyelination in MS.
Publisher
BioMed Central,BioMed Central Ltd,BMC
Subject
/ Anti-Bacterial Agents - toxicity
/ Biomedical and Life Sciences
/ Cell Differentiation - drug effects
/ Cell Differentiation - physiology
/ Demyelinating Diseases - chemically induced
/ Demyelinating Diseases - metabolism
/ Demyelinating Diseases - prevention & control
/ Gastrointestinal Microbiome - drug effects
/ Gastrointestinal Microbiome - physiology
/ Male
/ Mice
/ Microbiota (Symbiotic organisms)
/ Myelin Sheath - drug effects
/ Oligodendroglia - drug effects
/ Oligodendroglia - metabolism
