Butyrate inhibits interleukin-17 and generates Tregs to ameliorate colorectal colitis in rats

BMC Gastroenterol. 2016 Jul 30;16(1):84. doi: 10.1186/s12876-016-0500-x.

Abstract

Background: Butyrate is an energy source for colonocytes that is formed by bacterial fermentation of dietary fiber in the colon and that exerts broad anti-inflammatory activities. Although the administration of butyrate improves homeostasis in patients and ameliorates IBD (Inflammatory Bowel Disease)-related lesions and symptoms, the anti-inflammatory mechanisms of butyrate still remain unclear. To explore the impact of butyrate on Treg (Regulatory T cell)/Th17 (T helper 17 cell) differentiation and colitis in rats.

Methods: The effect of butyrate on the expression of markers related to both Tregs and Th17 cells were determined in human monocytes as well as a rat model of colitis induced by 2,4,6-trinitrobenzene sulfonic acid. Rats were treated with butyrate in vivo, whereas the rat splenocytes and human monocytes were treated in vitro.

Results: We found that butyrate administration increased peripheral blood Treg cell levels as well as plasma levels of anti-Th17 cytokines (IL-10 and IL-12). Butyrate administration further suppressed IL-17 levels in both plasma and colonic mucosa, and ameliorated colonic colitis lesions in rats. This promotion of Treg activity and inhibition of IL-17 release was also observed in human venous monocytes and rat splenocytes in vitro.

Conclusions: Our results suggest that butyrate plays a key role in regulating the Treg/Th17 balance and ultimately protects the colon mucosa against the development of IBD.

Keywords: Butyrate; Cytokines; Inflammatory bowel disease; Th17; Treg.

MeSH terms

  • Adult
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Body Weight
  • Butyrates / metabolism
  • Butyrates / pharmacology*
  • Cell Differentiation / drug effects*
  • Cells, Cultured
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / metabolism
  • Colitis, Ulcerative / pathology
  • Colon / pathology
  • Cytokines / blood
  • Disease Models, Animal
  • Fatty Acids, Volatile / metabolism
  • Female
  • Humans
  • Interleukin-17 / antagonists & inhibitors*
  • Male
  • Middle Aged
  • Rats, Sprague-Dawley
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / drug effects*

Substances

  • Anti-Inflammatory Agents
  • Butyrates
  • Cytokines
  • Fatty Acids, Volatile
  • Interleukin-17