A newly identified enzyme can break down gluten molecules before they reach the small intestine, Dutch researchers have shown, and may offer hope for the management of coeliac disease using oral supplements.
Coeliac disease is caused by an uncontrolled immune response to gluten, a protein found in wheat, rye and barley. Sufferers experience a wide range of symptoms including diarrhoea and malnutrition - the latter resulting from an inferior uptake of nutrients from food.
A Caucasian disease, it is known to be associated with the HLA-DQ2 gene. But while a quarter of the white population has this gene, only about one in 100 of these have the disease. The reason for this is not known.
Currently, the only way to manage the condition through avoidance of all products containing gluten - no easy feat since it is an ingredient commonly used by food manufacturers as a cheap protein, a binding agent and to improve the elasticity and stickiness of dough.
Although recognition of the disease is increasing and more gluten-free products are coming to market, if a dietary supplement were available that would prevent the gluten reaching the small intestine, where the immune response takes place, it would significantly improve the quality of life of sufferers.
Researchers from Leiden University in The Netherlands conducted the study using a prolyl endoprotease derived from a common fungus called Aspergillus niger (AN-PEP). It was originally developed for commercial food production; A. niger strains are used in production of citric acid and gluconic acid, and for the production of food grade enzymes.
A representative of DSM Food Specialities was also involved in the study.
The in vitro investigations showed that AN-PEP can almost completely break down whole gluten molecules and the T cell stimulatory peptides that cause coeliac disease.
In a paper published in the online American Journal of Physiology - Gastrointestinal and Liver Physiology, the researchers explain that destroying all or the vast majority of gluten derived T-cell stimulatory sequences is key to effective enzymatic management of the disease.
"The key to this is to break the large gluten molecules (large peptides and intact proteins) into smaller pieces before they leave the stomach," they wrote. "Because food stays in the stomach one to four hours, the speed of protein degradation is also important."
In the case of PEP, the pH environment in the stomach means that it works extremely quickly - about 60 times faster than another enzyme that has been studied for the same purpose in the past, prolyl oligopeptidases (POP).
On the basis of the results, lead researcher Frits Koning said: "There is now a realistic chance that oral supplementation with an enzyme can ensure gluten degradation in the stomach before reaching the small intestine."
The next stage in assessing the viability of AN-PEP in addressing coeliac disease will necessarily be human clinical trial involving sufferers, since there are no animal models for the disease.
"AN-PEP appears to be a prime candidate for such clinical trials," said Koning. "This is an option the team hopes to explore in the future."