Campylobacter concisus Impairs Sodium Absorption in Colonic Epithelium via ENaC Dysfunction and Claudin-8 Disruption

Int J Mol Sci. 2020 Jan 7;21(2):373. doi: 10.3390/ijms21020373.


The epithelial sodium channel (ENaC) can increase the colonic absorptive capacity for salt and water. Campylobacter concisus is a common pathogenic epsilonproteobacterium, causing enteritis and diarrhea. It can induce barrier dysfunction in the intestine, but its influence on intestinal transport function is still unknown. Therefore, our study aimed to characterize C. concisus effects on ENaC using the HT-29/B6-GR/MR (epithelial cell line HT-29/B6 transfected with glucocorticoid and mineralocorticoid receptors) cell model and mouse colon. In Ussing chambers, C. concisus infection inhibited ENaC-dependent Na+ transport as indicated by a reduction in amiloride-sensitive short circuit current (-55%, n = 15, p < 0.001). This occurred via down-regulation of β- and γ-ENaC mRNA expression and ENaC ubiquitination due to extracellular signal-regulated kinase (ERK)1/2 activation, predicted by Ingenuity Pathway Analysis (IPA). In parallel, C. concisus reduced the expression of the sealing tight junction (TJ) protein claudin-8 and induced claudin-8 redistribution off the TJ domain of the enterocytes, which facilitates the back leakage of Na+ ions into the intestinal lumen. In conclusion, C. concisus caused ENaC dysfunction via interleukin-32-regulated ERK1/2, as well as claudin-8-dependent barrier dysfunction-both of which contribute to Na+ malabsorption and diarrhea.

Keywords: claudin-8; diarrhea; epithelial sodium channel, extracellular signal-regulated kinase, Campylobacter concisus; sodium transport; tight junction.

MeSH terms

  • Animals
  • Campylobacter / physiology*
  • Campylobacter Infections / metabolism*
  • Campylobacter Infections / microbiology
  • Claudins / metabolism*
  • Colon / metabolism
  • Colon / microbiology
  • Diarrhea / metabolism
  • Diarrhea / microbiology
  • Epithelial Sodium Channels / metabolism*
  • HT29 Cells
  • Host-Pathogen Interactions
  • Humans
  • Intestinal Absorption
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Sodium / metabolism*


  • Claudins
  • Epithelial Sodium Channels
  • Sodium
  • claudin 8

Supplementary concepts

  • Campylobacter concisus