Alterations in intestinal permeability
The paracellular pathway between intestinal epithelial cells has become important in our understanding of gastrointestinal and systemic disease. Long thought to be a static non‐regulated barrier to the passage of luminal material, it is now recognised to be a dynamic constantly changing structure with a functional state that is carefully regulated. Luminal organisms can modulate the state of the tight junction through multiple mechanisms and while opening tight junctions may be of benefit for the microflora, it may be deleterious to the host. Abnormal function of this pathway can also be observed in conditions where the structure of the proteins comprising the junction is abnormal.
The functional state of the junction can be assessed by measuring the rate of movement of probes across the junction. This is what is referred to as gastrointestinal permeability testing and there are a variety of means to accomplish this either in vivo or in vitro. By carefully selecting the method used, it is possible to measure the permeability of various sites within the gastrointestinal tract.
For decades a variety of pathological states have been associated with abnormal permeability. Many of these are a consequence of intestinal epithelial damage that is associated with disease but not involved in a causal manner in the genesis of disease. However, in several autoimmune conditions it appears that increased permeability is a constant and early feature of the disease process. Furthermore, it is becoming increasingly apparent that in some conditions increased permeability is critical to the development of disease as if it is abrogated the disease does not develop. This is particularly true in type 1 diabetes. In other diseases such as Crohn’s disease or coeliac disease, a similar pattern of findings are apparent but the experiment to try and prevent disease by preventing the increase in permeability has not been performed.