Sodium Butyrate Inhibits Inflammation and Maintains Epithelium Barrier Integrity in a TNBS-induced Inflammatory Bowel Disease Mice Model

EBioMedicine. 2018 Apr:30:317-325. doi: 10.1016/j.ebiom.2018.03.030. Epub 2018 Mar 28.


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.

Keywords: Epithelium barrier; GPR109A; IBD; Inflammation; SB; TNBS.

MeSH terms

  • Animals
  • Butyric Acid / pharmacology
  • Butyric Acid / therapeutic use*
  • Caco-2 Cells
  • Colon / drug effects
  • Colon / pathology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Epithelium / drug effects
  • Epithelium / pathology*
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / pathology*
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / pathology*
  • Lipopolysaccharides
  • Macrophages, Peritoneal
  • Mice
  • Mice, Inbred C57BL
  • Mucin-2 / metabolism
  • Permeability
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • RAW 264.7 Cells
  • Signal Transduction / drug effects
  • Survival Analysis
  • Tight Junctions / drug effects
  • Tight Junctions / metabolism
  • Transcription Factor RelA / metabolism
  • Trinitrobenzenesulfonic Acid
  • Weight Loss / drug effects


  • Cytokines
  • Lipopolysaccharides
  • Mucin-2
  • Transcription Factor RelA
  • Butyric Acid
  • Trinitrobenzenesulfonic Acid
  • Proto-Oncogene Proteins c-akt