Tight junctions and IBS--the link between epithelial permeability, low-grade inflammation, and symptom generation?

Neurogastroenterol Motil. 2014 Mar;26(3):296-302. doi: 10.1111/nmo.12315.


In this issue of Neurogastroenterology and Motility, Dr Ewa Wilcz-Villega and colleagues report low expression of E-cadherin, a tight junction protein involved in the regulation of paracellular permeability, in the colonic mucosa of patients with the irritable bowel syndrome (IBS) with predominance of diarrhea (IBS-D) or alternating symptoms (IBS-A). These findings constitute an improvement in our knowledge of epithelial barrier disruption associated with IBS. There is mounting evidence to indicate that a compromised epithelial barrier is associated with low-grade immune activation and intestinal dysfunction in at least a proportion of IBS patients. During the last 10 years of research, much interest has focused on the increase in the number of different types of immune cells in the gut mucosa of IBS patients including: mast cells, T lymphocytes, and other local cells such as enteroendocrine cells. The inflammatory mediators released by these cells or other luminal factors could be at the origin of altered epithelial barrier functions and enteric nervous system signaling, which lead to gut hypersensitivity. A current conceptual framework states that clinical symptoms of IBS could be associated with structural and functional abnormalities of the mucosal barrier, highlighting the crucial importance of elucidating the contributory role of epithelial barrier defects in the pathogenesis of IBS. More importantly, disruption of the epithelial barrier could also participate in the generation of persistent abdominal pain and discomfort mimicking IBS in patients with inflammatory bowel diseases considered in remission. This mini review gives a brief summary of clinical and experimental evidence concerning the mechanisms underlying epithelial barrier defects in IBS.

Keywords: irritable bowel syndrome; mast cells; permeability; soluble factors; tight junctions.

Publication types

  • Review

MeSH terms

  • Epithelium / metabolism*
  • Humans
  • Immunity, Mucosal
  • Inflammation
  • Irritable Bowel Syndrome / immunology*
  • Irritable Bowel Syndrome / metabolism*
  • Permeability
  • Tight Junctions / metabolism*