An orally administered butyrate-releasing derivative reduces neutrophil recruitment and inflammation in dextran sulphate sodium-induced murine colitis

Br J Pharmacol. 2017 Jun;174(11):1484-1496. doi: 10.1111/bph.13637. Epub 2016 Nov 3.


Background and purpose: Butyrate has shown benefits in inflammatory bowel diseases. However, it is not often administered orally because of its rancid smell and unpleasant taste. The efficacy of a more palatable butyrate-releasing derivative, N-(1-carbamoyl-2-phenylethyl) butyramide (FBA), was evaluated in a mouse model of colitis induced by dextran sodium sulphate (DSS).

Experimental approach: Male 10 week-old BALB/c mice received DSS (2.5%) in drinking water (for 5 days) followed by DSS-free water for 7 days (DSS group). Oral FBA administration (42.5 mg·kg-1 ) was started 7 days before DSS as preventive (P-FBA), or 2 days after DSS as therapeutic (T-FBA); both treatments lasted 19 days. One DSS-untreated group received only tap water (CON).

Key results: FBA treatments reduced colitis symptoms and colon damage. P-FBA and T-FBA significantly decreased polymorphonuclear cell infiltration score compared with the DSS group. FBA reversed the imbalance between pro- and anti-inflammatory cytokines (reducing inducible NOS protein expression, CCL2 and IL-6 transcripts in colon and increasing TGFβ and IL-10). Morever, P-FBA and T-FBA limited neutrophil recruitment (by expression and localization of the neutrophil granule protease Ly-6G), restored deficiency of the butyrate transporter and improved intestinal epithelial integrity, preventing tight-junction impairment (zonulin-1 and occludin). FBA, similar to its parental compound sodium butyrate, inhibited histone deacetylase-9 and restored H3 histone acetylation, exerting an anti-inflammatory effect through NF-κB inhibition and the up-regulation of PPARγ.

Conclusions and implications: FBA reduces inflammatory intestinal damage in mice indicating its potential as a postbiotic derivative without the problems associated with the oral administration of sodium butyrate.

Linked articles: This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Butyrates / administration & dosage
  • Butyrates / pharmacology*
  • Colitis / drug therapy*
  • Colitis / pathology
  • Colitis / prevention & control
  • Dextran Sulfate / toxicity
  • Disease Models, Animal
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / antagonists & inhibitors
  • Neutrophil Infiltration / drug effects
  • PPAR gamma / genetics
  • Time Factors
  • Up-Regulation / drug effects


  • Anti-Inflammatory Agents
  • Butyrates
  • N-(1-carbamoyl-2-phenyl-ethyl)butyramide
  • NF-kappa B
  • PPAR gamma
  • Dextran Sulfate