A unified hypothesis of coeliac disease with implications for management of patients.

This mini-review presents the research carried out within the context of two of the main hypotheses of the aetiology of coeliac disease. The enzymopathic hypothesis of the disease has been placed clearly as the underlying deficiency causing increased levels of toxic peptides, while the immunological hypothesis has been implicated in the pathogenesis of the disorder as the result of the action of undigested peptides in the small intestine. As a consequence, we are proposing a unified hypothesis of coeliac disease, which takes into account the actions of these undigested peptides through their direct cytotoxicity and their immunoactivity. At the same time, work aimed at defining some of these biologically active peptides, which could be said to be involved in the aetiopathogenesis of coeliac disease, will be reported. The review also focusses on the use of enzyme therapy for management of the disease, which when used in conjunction with the gluten-free diet, offers a safeguard against damage to the small intestine caused by small amounts of gluten.