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Cited by 330Neuroinflammation and Neurodegeneration MechanismsGut microbiota and healthTryptophan and brain disorders

Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated With Aging in Mice

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Matt, Stephanie M., Allen, Jacob M., Lawson, Marcus A., Mailing, Lucy J., Woods, Jeffrey A., Johnson, Rodney W.·2018·Frontiers in Immunology
DOI 10.3389/fimmu.2018.01832PMC PMC6102557
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Abstract

Aging results in chronic systemic inflammation that can alter neuroinflammation of the brain. Specifically, microglia shift to a pro-inflammatory phenotype predisposing them to hyperactivation upon stimulation by peripheral immune signals. It is proposed that certain nutrients can delay brain aging by preventing or reversing microglial hyperactivation. Butyrate, a short-chain fatty acid (SCFA) produced primarily by bacterial fermentation of fiber in the colon, has been extensively studied pharmacologically as a histone deacetylase inhibitor and serves as an attractive therapeutic candidate, as butyrate has also been shown to be anti-inflammatory and improve memory in animal models. In this study, we demonstrate that butyrate can attenuate pro-inflammatory cytokine expression in microglia in aged mice. It is still not fully understood, however, if an increase in butyrate-producing bacteria in the gut as a consequence of a diet high in soluble fiber could affect microglial activation during aging. Adult and aged mice were fed either a 1% cellulose (low fiber) or 5% inulin (high fiber) diet for 4 weeks. Findings indicate that mice fed inulin had an altered gut microbiome and increased butyrate, acetate, and total SCFA production. In addition, histological scoring of the distal colon demonstrated that aged animals on the low fiber diet had increased inflammatory infiltrate that was significantly reduced in animals consuming the high fiber diet. Furthermore, gene expression of inflammatory markers, epigenetic regulators, and the microglial sensory apparatus (i.e., the sensome) were altered by both diet and age, with aged animals exhibiting a more anti-inflammatory microglial profile on the high fiber diet. Taken together, high fiber supplementation in aging is a non-invasive strategy to increase butyrate levels, and these data suggest that an increase in butyrate through added soluble fiber such as inulin could counterbalance the age-related microbiota dysbiosis, potentially leading to neurological benefits.

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  • Targeting microglia could present an interventional approach to ameliorate neurodegenerative disease.

    “Such studies suggest that targeting microglia could present an interventional approach to ameliorate neurodegenerative disease”

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Authors
Matt, S. M., Allen, J. M., Lawson, M. A., Mailing, L. J., Woods, J. A., & Johnson, R. W.
Affiliations
University of Illinois Urbana-Champaign (US)
Corresponding author
Johnson, Rodney W.
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2018-08-14
Volume
9
Pages
1832-1832
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2018.01832
PMC
PMC6102557
OpenAlex
W2886360969
Cited by
330
References
9
Citations by year
2026: 36 · 2025: 49 · 2024: 46 · 2023: 40 · 2022: 41 · 2021: 62 · 2020: 36 · 2019: 20
FWCI
13.27
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (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, cc-by-sa)
Funders
Foundation for the National Institutes of Health (R01 AG16710)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
butyrate, soluble dietary fiber, inulin, neuroinflammation, brain aging, microglial activation, short-chain fatty acids, gut microbiota, dysbiosis, inflammatory cytokines, histone deacetylase, acetate, colonic inflammation, dietary supplementation
MeSH terms
Gastrointestinal Microbiome, Aging, Animals, Butyrates, Dietary Fiber, Disease Models, Animal, Encephalitis, Gene Expression Regulation, Hippocampus, Lipopolysaccharides, Microglia, Tight Junctions, DNA Methylation, Epigenesis, Genetic, Mice, Interleukin-1beta

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