Inhibition of inflammatory microglia by dietary fiber and short-chain fatty acids
Open accessAbstract
Microglia play a vital role maintaining brain homeostasis but can also cause persistent neuroinflammation. Short-chain fatty acids (SCFAs) produced by the intestinal microbiota have been suggested to regulate microglia inflammation indirectly by signaling through the gut-brain axis or directly by reaching the brain. The present work evaluated the anti-inflammatory effects of SCFAs on lipopolysaccharide (LPS)-stimulated microglia from mice fed inulin, a soluble fiber that is fermented by intestinal microbiota to produce SCFAs in vivo, and SCFAs applied to primary microglia in vitro. Feeding mice inulin increased SCFAs in the cecum and in plasma collected from the hepatic portal vein. Microglia isolated from mice fed inulin and stimulated with LPS in vitro secreted less tumor necrosis factor α (TNF-α) compared to microglia from mice not given inulin. Additionally, when mice were fed inulin and injected i.p with LPS, the ex vivo secretion of TNF-α by isolated microglia was lower than that secreted by microglia from mice not fed inulin and injected with LPS. Similarly, in vitro treatment of primary microglia with acetate and butyrate either alone or in combination downregulated microglia cytokine production with the effects being additive. SCFAs reduced histone deacetylase activity and nuclear factor-κB nuclear translocation after LPS treatment in vitro. Whereas microglia expression of SCFA receptors Ffar2 or Ffar3 was not detected by single-cell RNA sequencing analysis, the SCFA transporters Mct1 and Mct4 were. Nevertheless, inhibiting monocarboxylate transporters on primary microglia did not interfere with the anti-inflammatory effects of SCFAs, suggesting that if SCFAs produced in the gut regulate microglia directly it is likely through an epigenetic mechanism following diffusion.
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Acetate and butyrate inhibit the inflammatory response of LPS-stimulated primary microglia by inhibiting HDAC activity and NF-κB activation.
“Acetate and butyrate have been shown to inhibit the inflammatory response of LPS-stimulated primary microglia by inhibiting HDAC activity and NF-κB activation.289”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [289]
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Immune Remodeling during Aging and the Clinical Significance of Immunonutrition in Healthy Aging
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The early life exposome and autism risk: a role for the maternal microbiome?
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The Microbiome–Genetics Axis in Autism Spectrum Disorders: A Probiotic Perspective
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Frataxin deficiency shifts metabolism to promote reactive microglia via glucose catabolism
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Peripheral immune and metabolic regulation of Aβ and Tau by exercise in Alzheimer’s disease
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The role of the gut microbiome in neuroinflammation and chemotherapy-induced peripheral neuropathy
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Early Life Stress and Gut Microbiome Dysbiosis: A Narrative Review
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Amyloid-β-driven Alzheimer’s disease reshapes the colonic immune system in mice
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The Metabolomic Mind: Microbial Metabolite Programming of Microglia
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Gut Microbiome as a Source of Probiotic Drugs for Parkinson’s Disease
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Parallel Pathways, Divergent Outcomes: Adipose Tissue–Neural Crosstalk in Depression and Obesity
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The role of carbohydrates in canine and feline nutrition
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Unlocking the neuroprotective secrets of natural products: a focus on the gut-brain axis
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Gut microbiota is necessary for pair-housing to protect against post-stroke depression in mice
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Does the Maternal Gut Microbiome Influence the Outcome of Perinatal Asphyxia?
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- Authors
- Caetano-Silva, M. E., Rund, L., Hutchinson, N. T., Woods, J. A., Steelman, A. J., & Johnson, R. W.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Johnson, Rodney W.
- Venue
- Scientific Reports
- Published
- 2023-02-16
- Volume
- 13
- Issue
- 1
- Pages
- 2819-2819
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC9935636
- OpenAlex
- W4321018263
- Cited by
- 225
- References
- 32
- Citations by year
- 2026: 80 · 2025: 77 · 2024: 51 · 2023: 17
- FWCI
- 23.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (R01 AG059622)
- 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
- microglia, neuroinflammation, short-chain fatty acids, dietary fiber, inulin, gut microbiota, lipopolysaccharide, TNF-α, acetate, butyrate, histone deacetylase, NF-κB, FFAR2, FFAR3, MCT1, MCT4, monocarboxylate transporters, epigenetic regulation, gut-brain axis
- MeSH terms
- Animals, Anti-Inflammatory Agents, Dietary Fiber, Fatty Acids, Volatile, Inulin, Lipopolysaccharides, Tumor Necrosis Factor-alpha, Microglia, Membrane Transport Proteins, Mice
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