KIMBALL, Neb. – Celiac disease (CD) and gluten sensitivity have been much in the news over the past few years. According to Centers for Disease Control (CDC) and National Institutes of Health (NIH) statistics, diagnoses of celiac disease have been slowly but steadily rising since about the year 2000.

Celiac disease is defined as a genetically-predisposed autoimmune inflammatory disease which causes damage to the small intestine. One of the most common forms of food intolerance worldwide, the disease affects predominantly Europeans and those of European ancestry. In the U.S. about one in 111 people have the disease, which accounts for roughly one percent of the population. The primary trigger for celiac disease is eating cereal grains such as wheat, rye, barley, and to a lesser extent, oats. The direct cause of autoimmune response in those with the disease is an intolerance for certain protein epitopes present in gluten. In essence, the body reacts to the presence of these epitopes with an immune response which actually attacks the lining of the small intestine.

Gluten is, of course, a complex mixture of proteins present in cereal grains. When flour is mixed with water, the protein strands swell and form long chains. Mixing or kneading “develops” the gluten, which gives bread dough its elasticity. This elasticity allows bread to “rise” by trapping bubbles of carbon dioxide within the dough matrix.

With an apparent increase in CD over the last couple of decades, and obvious question is why. Why the increase? Has something changed to cause it?

As Alex Berezow of the American Council of Science and Health (ACSH) noted earlier this month, “Several explanations are possible for what appears to be an increase in celiac disease and/or gluten sensitivity. For instance, perhaps human immunogenetics have changed over time due to some unknown evolutionary selective pressure. Alternatively, it is possible that our dietary habits have influenced our immune system, in the same way that our hygienic habits have been linked to an increase in allergies and autoimmune disorders. Or, perhaps there is no increase at all; more people are being diagnosed simply because doctors are now aware the condition exists.”

The apparent uptick in diagnosis of celiac disease has led to the theory that wheat breeding programs have unintentionally caused an increase in the disease by producing wheat which contains more of the problematic gluten protein epitopes. Wheat breeding programs have been producing strains with improved traits for more than a century, and while these improvements include higher yield, disease resistance and drought tolerance, they also include improvements in quantity and quality of gluten to improve bakeability, texture and taste, mouthfeel, and other consumer-desired qualities.

The notion that wheat breeding programs may be causing increases in celiac disease is an attractive theory because improvements in gluten quality and quantity could have unintentionally increased the epitopes of concern. This in turn could explain the uptick in disease as well as provide a potential avenue for development of wheat strains which do not cause the autoimmune response in celiac disease.

Indeed, studies done in the Netherlands in 2010 and 2015 by Dutch scientists van den Broeck, Cordewener, Nessen, and van der Meer indeed showed an increase in problematic epitopes in three varieties of Dutch wheat. The oldest variety showed the fewest problem epitopes and the newest variety showed the most, indicating that the problem is increasing over time. As noted, however, the study was limited to three varieties only, which makes for a very small and limited sample size. Other studies have shown that older, landrace wheat cultivars often contain higher levels of problem epitopes than newer cultivars produced through various wheat breeding programs.

A recent study (2018) in the peer reviewed journal Food Chemistry provides evidence that the presence of problem epitopes in wheat varieties is likely not related to wheat breeding efforts after all.

In their paper, “Detection and quantitation of immunogenic epitopes related to celiac disease in historical in modern hard red spring wheat cultivars,” North Dakota State researchers Maneka Malalgoda, Steven W. Meinhardt, and Sinay Simsek studied thirty cultivars released in North Dakota between 1910 and 2013.

After preparing samples of each cultivar the researchers used High Performance Liquid Chromatography (HPLC) to determine how gluten profiles changed in relation to individual cultivar release year over time. They then performed mass spectrographic analysis on samples from each cultivar to determine if immunogenic epitopes causing celiac disease were present in the cultivars studied, and if so, to quantify their presence.

“Overall,” concluded Malalgoda et al., “the results indicate that immunogenic epitopes causing celiac disease (response) are present in historical and modern cultivars irrespective of release year, and that the quantity of these epitopes does not show a relationship with cultivar release year, indicating that modern cultivars are not higher in CD antigenicity in comparison to historical wheat cultivars.”

In essence, this more comprehensive study indicates that wheat breeding programs are not inadvertently causing an increase in celiac disease by accidentally increasing problem gluten epitopes over time. Celiac disease remains an autoimmune disease where affected individuals atypically (compared to those who do not have the disorder) suffer an immune response when eating cereal grains containing immunogenic gluten epitopes.

The study also revealed that a number of wheat cultivars appear to be naturally very low in the problem gluten epitopes, and this opens the door to breeding new cultivars of wheat which CD sufferers might be able to eat safely.

Regarding non-celiac gluten sensitivity, it is not precisely a disease. In general, those who feel they are sensitive to gluten -- for whatever reason -- report various symptoms of abdominal discomfort when eating gluten containing foods and an easing or absence of symptoms when not eating gluten. To date, no scientific study has proven an actual mechanism for gluten sensitivity. Double-blinded, randomized, and placebo-controlled studies show that subjects who described having common symptoms of gluten sensitivity, that is, abdominal pain, bloating, nausea, and gas, suffered from identical symptoms even when eating a placebo diet containing no gluten at all.

How can this be? One explanation is the “nocebo effect,” a largely psychogenic effect similar to the placebo effect. In the placebo effect, people who expect to feel better after taking a medicine tend to feel better, even when given a placebo instead of actual medicine. In the nocebo effect, people who expect a negative outcome from an experience -- such as abdominal symptoms after eating gluten -- tend to experience a negative effect even when given a non-gluten placebo meal instead of one containing gluten.

Both celiac disease and gluten sensitivity are interesting topics worthy of further study, but increasingly solid evidence shows that wheat breeding efforts are unlikely to be the cause. On the upside, continued wheat breeding progress may end up triumphing over celiac disease, and perhaps, even over gluten sensitivity.