The goal of this review is to describe barrier function of the intestine, the structure of the tight junction, methods to evaluate intestinal permeability, and most importantly the relevance of abnormal permeability to disease. In this context, we will also present an emerging paradigm regarding the genesis of autoimmune diseases and describe the data that supports this from the perspective of both human disease and animal models. While this is a complicated area there are several points worth remembering:

• epithelial permeability of the gastrointestinal tract can be evaluated in a site specific manner;

• increased intestinal permeability is observed in association with several autoimmune diseases. It is observed prior to disease and appears to be involved in disease pathogenesis;

• there are new and novel therapies directed at altering abnormally increased intestinal permeability and these may play a role in treating or preventing these diseases.

BARRIER FUNCTION

From the lower oesophageal sphincter to the anus, the gastrointestinal tract has a single contiguous layer of cells that separates the inside of the body from the external environment. Separation is important as there are a wide variety of environmental agents in the lumen of the bowel that can initiate or perpetuate mucosal inflammation if they cross the epithelial barrier. While the epithelial lining of the intestine plays a critical role in preventing access of these agents, it is not the only component of what is termed barrier function. Also important are secreted products such as immunoglobulin, mucous, defensins, and other antimicrobial products.

The importance of epithelial barrier function in normal homeostasis can be appreciated from experiments performed in the early 1990s where cell wall extracts from luminal bacteria were injected into the colonic wall of rats.¹ This simple manoeuvre of bypassing the epithelial barrier and placing luminal compounds directly into the colonic wall initiated an …