Celiac breakthrough

Celiac disease is an autoimmune disorder, where gluten triggers the immune system to attack the gut. It is common, lifelong and can seriously harm health – but nobody knows for sure what causes it.

Now a review in the journal Frontiers in Pediatrics says a common food additive could both cause and trigger these autoimmune attacks, and calls for warnings on food labels pending further tests.

ENVIRONMENT CAUSES CELIAC DISEASE – BUT ONLY IN SUSCEPTIBLE INDIVIDUALS
Gluten-free diets have become popular despite little or no evidence of benefit for most people. But for the one in 100 with celiac disease, even a mouthful of bread can trigger an immune response that damages the small intestine, impairing nutrient absorption.

Just what causes this autoimmune reaction to gluten – a protein found in wheat, rye and barley – is uncertain. Specific mutations in an important immunity-related gene called HLA-DQ seem to be necessary for developing celiac disease, with one of two HLA-DQ variants present in virtually every sufferer – but insufficient, as these variants are also present in about 30 per cent of the general population.

As a result, many environmental factors have proposed to interact with genetic risk to cause celiac disease. These include infections, food and toxins, vaccination, drugs and surgery. Most recently, food additives have been suggested to contribute. Among these, microbial transglutaminase – a bacterial enzyme heavily used in the industrial processing of meat, dairy, baked and other food products – has emerged as a likely culprit, according to the new review.

HOW A FOOD BINDER COULD BE OUR UNDOING
“Microbial transglutaminase can glue together proteins, so it’s used to improve food texture, palatability and shelf life,” says co-author Aaron Lerner, visiting professor at the Aesku.Kipp Institute in Germany. “This enzyme functions like the transglutaminase produced by our body, which is known to be the target of autoimmunity in celiac disease.”

There is a direct positive correlation between rising use of industrial enzymes in bakery products and rising incidence of celiac disease in the last four decades, according to Lerner and co-author Matthias Torsten of the Aesku.KIPP Institute, Germany. But if transglutaminase is produced normally in our tissues – and by our own gut microbes – what difference should a little more in our diet make?

WHAT LINKS GLUTEN, TRANSGLUTAMINASE, HLA-DQ GENES AND AUTOIMMUNITY?
Gluten is tough to break down completely, which can help baked goods rise and keep their shape, but in celiac sufferers presents a problem and a possible causal link with microbial transglutaminase.

“The gluten protein fragments or ‘peptides’ that remain after digestion are highly susceptible to transglutaminase, which modifies them to make a variety of new peptides,” Lerner explains. “These un
usual peptides are particularly likely to resist further breakdown, and to be recognized as ‘foreign’ by HLA-DQ immune receptors inside the gut wall – but only in those carrying the HLA-DQ variants associated with celiac disease.”

HUMAN STUDIES IMPLICATE MICROBIAL TRANSGLUTAMINASE
This all begs the question: if it is gluten-derived proteins that stimulate immune cells in celiac disease, why does the immune response target transglutaminase? And are microbial and human transglutaminase recognized interchangeably by the immune system?

Microbial transglutaminase (bound to gluten fragments) could in fact be the target of the immune response in celiac disease – and the attack on our own transglutaminase merely a case of mistaken identity. Microbial transglutaminase present in processed foods is therefore a potential environmental cause of celiac disease.

IS this food binder SAFE?
But according to Lerner, the jury is still out. “Ultimately all we have so far are associations between microbial transglutaminase and celiac disease. To test whether this enzyme causes or triggers immune damage in celiac disease will require experimenting with exposure in animal models, intestinal cell lines or biopsies.”

With no known cure for celiac disease, treatment depends on preventive measures, namely, following a gluten-free diet.

“Until there is a clearer answer, we recommend transparency and vigilance with regards to labeling of foods processed using microbial transglutaminase,” he says •

Read the original study: frontiersin.org/articles/10.3389/fped.2018.00389/full