Abnormal intestinal permeability in Crohn's disease pathogenesis

Ann N Y Acad Sci. 2012 Jul;1258:159-65. doi: 10.1111/j.1749-6632.2012.06612.x.

Abstract

Increased small intestinal permeability is a longstanding observation in both Crohn's disease patients and in their healthy, asymptomatic first-degree relatives. However, the significance of this compromised gut barrier function and its place in the pathogenesis of the disease remains poorly understood. The association between abnormal small intestinal permeability and a specific mutation in the NOD2 gene, which functions to modulate both innate and adaptive immune responses to intestinal bacteria, suggests a common, genetically determined pathway by which an abnormal gut barrier could result in chronic intestinal inflammation. Furthermore, rodent colitis models show that gut barrier defects precede the development of inflammatory changes. However, it remains possible that abnormal permeability is simply a consequence of mucosal inflammation. Further insight into whether abnormal barrier function is the cause or consequence of chronic intestinal inflammation will be crucial to understanding the role of intestinal permeability in the pathogenesis of Crohn's disease.

MeSH terms

  • Crohn Disease / genetics
  • Crohn Disease / physiopathology*
  • Humans
  • Intestinal Absorption*
  • Nod2 Signaling Adaptor Protein / genetics

Substances

  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein