G-protein coupled receptor 35 (GPR35) regulates the colonic epithelial cell response to enterotoxigenic Bacteroides fragilis

Commun Biol. 2021 May 14;4(1):585. doi: 10.1038/s42003-021-02014-3.


G protein-coupled receptor (GPR)35 is highly expressed in the gastro-intestinal tract, predominantly in colon epithelial cells (CEC), and has been associated with inflammatory bowel diseases (IBD), suggesting a role in gastrointestinal inflammation. The enterotoxigenic Bacteroides fragilis (ETBF) toxin (BFT) is an important virulence factor causing gut inflammation in humans and animal models. We identified that BFT signals through GPR35. Blocking GPR35 function in CECs using the GPR35 antagonist ML145, in conjunction with shRNA knock-down and CRISPRcas-mediated knock-out, resulted in reduced CEC-response to BFT as measured by E-cadherin cleavage, beta-arrestin recruitment and IL-8 secretion. Importantly, GPR35 is required for the rapid onset of ETBF-induced colitis in mouse models. GPR35-deficient mice showed reduced death and disease severity compared to wild-type C57Bl6 mice. Our data support a role for GPR35 in the CEC and mucosal response to BFT and underscore the importance of this molecule for sensing ETBF in the colon.

Publication types

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

MeSH terms

  • Animals
  • Bacterial Toxins / administration & dosage*
  • Bacteroides fragilis / genetics
  • Bacteroides fragilis / metabolism
  • Bacteroides fragilis / pathogenicity*
  • Colitis / etiology
  • Colitis / metabolism
  • Colitis / pathology*
  • Colon / drug effects
  • Colon / metabolism
  • Colon / microbiology
  • Colon / pathology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology
  • Epithelial Cells / pathology*
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / microbiology
  • Gastrointestinal Tract / pathology*
  • Metalloendopeptidases / administration & dosage*
  • Mice
  • Mice, Inbred C57BL
  • Receptors, G-Protein-Coupled / physiology*


  • Bacterial Toxins
  • GPR35 protein, mouse
  • Receptors, G-Protein-Coupled
  • Bacteroides fragilis toxin
  • Metalloendopeptidases