Butyrate suppresses demyelination and enhances remyelination
Open accessAbstract
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.
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Treatment with butyrate suppresses demyelination and enhances remyelination through oligodendrocyte maturation and differentiation.
“Furthermore, treatment with butyrate suppresses demyelination and enhances remyelination through oligodendrocyte maturation and differentiation (180).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [180]
Beneficial effects of butyrate on oligodendrocytes are evident in cuprizone- and lysolecithin-induced demyelination.
“The beneficial effects of butyrate on oligodendrocytes are similarly evident in cuprizone- and lysolecithin-induced demyelination.266”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [266]
Short-chain fatty acids favor enhancement of acetyl-CoA metabolism, histone acetylation, preservation of spinal cord lipid content, suppression of demyelination, and oligodendrocyte maturation and differentiation.
“Mechanistically, SCFAs favor the enhancement of acetyl-CoA metabolism, histone acetylation, preservation of spinal cord lipid content, suppression of demyelination, oligodendrocyte maturation and differentiation (157, 158).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [158]
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- Authors
- Chen, T., Noto, D., Hoshino, Y., Mizuno, M., & Miyake, S.
- Affiliations
- Juntendo University (JP)
- Corresponding author
- Noto, Daisuke
- Miyake, Sachiko
- Venue
- Journal of Neuroinflammation
- Published
- 2019-08-09
- Volume
- 16
- Issue
- 1
- Pages
- 165-165
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC6688239
- OpenAlex
- W2968259240
- Cited by
- 229
- References
- 61
- Citations by year
- 2026: 21 · 2025: 37 · 2024: 42 · 2023: 30 · 2022: 40 · 2021: 31 · 2020: 23 · 2019: 5
- FWCI
- 18.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Japan Agency for Medical Research and Development (18ek0109189s0103)
- Japan Society for the Promotion of Science (17H04218)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- butyrate, short-chain fatty acids, demyelination, remyelination, multiple sclerosis, gut microbiota, cuprizone, lysophosphatidylcholine, oligodendrocyte differentiation, microglia, organotypic slice cultures, antibiotic-induced dysbiosis
- MeSH terms
- Gastrointestinal Microbiome, Remyelination, Animals, Anti-Bacterial Agents, Butyrates, Cell Differentiation, Cuprizone, Demyelinating Diseases, Male, Mice, Inbred C57BL, Myelin Sheath, Oligodendroglia, Organ Culture Techniques, Mice
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