A Common Mechanism Links Activities of Butyrate in the Colon

ACS Chem Biol. 2018 May 18;13(5):1291-1298. doi: 10.1021/acschembio.8b00073. Epub 2018 Apr 10.


Two biological activities of butyrate in the colon (suppression of proliferation of colonic epithelial stem cells and inflammation) correlate with inhibition of the activity of histone deacetylases. Cellular and biochemical studies of molecules similar in structure to butyrate, but different in molecular details (functional groups, chain-length, deuteration, oxidation level, fluorination, or degree of unsaturation), demonstrated that these activities were sensitive to molecular structure, and were compatible with the hypothesis that butyrate acts by binding to the Zn2+ in the catalytic site of histone deacetylases. Structure-activity relationships drawn from a set of 36 compounds offer a starting point for the design of new compounds targeting the inhibition of histone deacetylases. The observation that butyrate was more potent than other short-chain fatty acids is compatible with the hypothesis that crypts evolved (at least in part), to separate stem cells at the base of crypts from butyrate produced by commensal bacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Butyrates / metabolism*
  • Cell Proliferation / drug effects
  • Colon / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylases / metabolism
  • Humans
  • Inflammation / prevention & control
  • Interleukin-6 / metabolism
  • Intestinal Mucosa / metabolism
  • Macrophages / metabolism
  • Oxidation-Reduction


  • Butyrates
  • Histone Deacetylase Inhibitors
  • Interleukin-6
  • Histone Deacetylases