Exorphins

Gluten intake is associated with the development of celiac disease (CD) and related disorders such as diabetes mellitus type I, depression, and schizophrenia. However, until now, there is no consent about the possible deleterious effects of gluten intake because of often failing symptoms even in persons with proven CD. Asymptomatic CD (ACD) is present in the majority of affected patients and is characterized by the absence of classical gluten-intolerance signs, such as diarrhea, bloating, and abdominal pain. Nevertheless, these individuals very often develop diseases that can be related with gluten intake. Gluten can be degraded into several morphine-like substances, named gluten exorphins. These compounds have proven opioid effects and could mask the deleterious effects of gluten protein on gastrointestinal lining and function. Here we describe a putative mechanism, explaining how gluten could mask its own toxicity by exorphins that are produced through gluten protein digestion. The precise pathway leading to the development of ACD still needs to be discovered. However, the putative mechanism presented in this review could explain this intruding phenomenon. The incomplete breakdown of the gluten protein, resulting in the presence of gliadin peptides with opioid effects, makes it plausible to suggest that the opioid effects of gluten exorphins could be responsible for the absence of classical gastrointestinal symptoms of individuals suffering from gluten-intake-associated diseases. Moreover, the partial digestion of gluten, leading to DPP IV inhibition, could also account for the presence of extra-intestinal symptoms and disorders in ACD and the occurrence of intestinal and extra-intestinal symptoms and disorders in CD and NCGS patients. If so, then individuals suffering from any of these conditions should be recognized in time and engage in a gluten-free lifestyle to prevent gluten-induced symptoms and disorders.