Sodium Butyrate Inhibits Inflammation and Maintains Epithelium Barrier Integrity in a TNBS-induced Inflammatory Bowel Disease Mice Model
Open accessAbstract
G Protein Coupled Receptor 109A (GPR109A), which belongs to the G protein coupled receptor family, can be activated by niacin, butyrate, and β-hydroxybutyric acid. Here, we assessed the anti-inflammatory activity of sodium butyrate (SB) on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis mice, an experimental model that resembles Crohn's disease, and explored the potential mechanism of SB in inflammatory bowel disease (IBD). In vivo , experimental GPR109a −/− and wild-type ( WT ) mice were administered SB (5g/L) in their drinking water for 6weeks. The mice were then administered TNBS via rectal perfusion to imitate colitis. In vitro , RAW246.7 macrophages, Caco-2 cells, and primary peritoneal macrophages were used to investigate the protective roles of SB on lipopolysaccharide (LPS)-induced inflammatory response and epithelium barrier dysfunction. In vivo , SB significantly ameliorated the inflammatory response and intestinal epithelium barrier dysfunction in TNBS-induced WT mice, but failed to provide a protective effect in TNBS-induced GPR109a −/− mice. In vitro , pre-treatment with SB dramatically inhibited the expression of TNF-α and IL-6 in LPS-induced RAW246.7 macrophages. SB inhibited the LPS-induced phosphorylation of the NF-κB p65 and AKT signaling pathways, but failed to inhibit the phosphorylation of the MAPK signaling pathway. Our data indicated that SB ameliorated the TNBS-induced inflammatory response and intestinal epithelium barrier dysfunction through activating GPR109A and inhibiting the AKT and NF-κB p65 signaling pathways. These findings therefore extend the understanding of GPR109A receptor function and provide a new theoretical basis for treatment of IBD.
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Butyrate exerts anti-inflammatory and anti-oxidant effects while repairing the intestinal barrier.
“Butyrate exerts anti-inflammatory and [18] anti-oxidant effects [19] while repairing the intestinal barrier [20].”
From Neuroprotective Effects of Sodium Butyrate by Restoring Gut Microbiota and Inhibiting TLR4 Signaling in Mice with MPTP-Induced Parkinson’s Disease (2023) · cites this paper as [20]
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- Authors
- Chen, G., Ran, X., Li, B., Li, Y., He, D., Huang, B., Fu, S., Liu, J., & Wang, W.
- Affiliations
- Jilin University (CN)
- First Hospital of Jilin University (CN)
- Corresponding author
- Liu, Juxiong
- Wang, Wei
- Venue
- eBioMedicine
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 30
- Pages
- 317-325
- ISSN
- 2352-3964 (ISSN-L)
- PMC
- PMC5952406
- OpenAlex
- W2794833162
- Cited by
- 580
- References
- 54
- Citations by year
- 2026: 69 · 2025: 102 · 2024: 108 · 2023: 95 · 2022: 75 · 2021: 64 · 2020: 38 · 2019: 21 · 2018: 7
- FWCI
- 19.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- EBioMedicine (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Jilin University
- National Aerospace Science Foundation of China
- Graduate Student's Research and Innovation Fund of Sichuan University (2017168)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- sodium butyrate, GPR109A, inflammatory bowel disease, TNBS-induced colitis, Crohn's disease, intestinal epithelial barrier, NF-κB p65 signaling, Akt signaling, lipopolysaccharide-induced inflammation, macrophages, Caco-2 cells, anti-inflammatory activity
- MeSH terms
- RAW 264.7 Cells, Animals, Colon, Disease Models, Animal, Epithelium, Humans, Inflammation, Lipopolysaccharides, Mice, Inbred C57BL, Permeability, Phosphorylation, Trinitrobenzenesulfonic Acid, Inflammatory Bowel Diseases, Signal Transduction, Weight Loss, Survival Analysis, Cytokines, Macrophages, Peritoneal, Caco-2 Cells, Tight Junctions, Butyric Acid, Proto-Oncogene Proteins c-akt, Mice, Transcription Factor RelA, Mucin-2
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