Microbial-Derived Butyrate Promotes Epithelial Barrier Function through IL-10 Receptor-Dependent Repression of Claudin-2

J Immunol. 2017 Oct 15;199(8):2976-2984. doi: 10.4049/jimmunol.1700105. Epub 2017 Sep 11.


Commensal interactions between the enteric microbiota and distal intestine play important roles in regulating human health. Short-chain fatty acids (SCFAs), such as butyrate, produced through anaerobic microbial metabolism represent a major energy source for the host colonic epithelium and enhance epithelial barrier function through unclear mechanisms. Separate studies revealed that the epithelial anti-inflammatory IL-10 receptor α subunit (IL-10RA) is also important for barrier formation. Based on these findings, we examined if SCFAs promote epithelial barrier through IL-10RA-dependent mechanisms. Using human intestinal epithelial cells (IECs), we discovered that SCFAs, particularly butyrate, enhanced IEC barrier formation, induced IL-10RA mRNA, IL-10RA protein, and transactivation through activated Stat3 and HDAC inhibition. Loss and gain of IL-10RA expression directly correlates with IEC barrier formation and butyrate represses permeability-promoting claudin-2 tight-junction protein expression through an IL-10RA-dependent mechanism. Our findings provide a novel mechanism by which microbial-derived butyrate promotes barrier through IL-10RA-dependent repression of claudin-2.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Bacteria, Anaerobic / physiology*
  • Butyrates / immunology
  • Butyrates / metabolism*
  • Cell Line
  • Cells, Cultured
  • Claudin-2 / metabolism
  • Colon / pathology*
  • Gastrointestinal Microbiome / immunology*
  • Gene Expression Regulation
  • Histone Deacetylases / metabolism
  • Humans
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / physiology*
  • Receptors, Interleukin-10 / genetics
  • Receptors, Interleukin-10 / metabolism*
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Symbiosis
  • Tight Junctions / metabolism*
  • Transcriptional Activation
  • Transendothelial and Transepithelial Migration
  • Up-Regulation


  • Butyrates
  • Claudin-2
  • Receptors, Interleukin-10
  • STAT3 Transcription Factor
  • Histone Deacetylases