Making Wheat Safe for People with Celiac Disease: A New Genetic Breakthrough

Celiac.com 07/11/2025 - Celiac disease is an immune condition that affects around 1 in 100 people worldwide. It is triggered when genetically susceptible individuals consume gluten—a group of proteins found in wheat, barley, and rye. These proteins, particularly parts of wheat called gliadins and glutenins, contain small sequences of amino acids known as epitopes. In people with celiac disease, these epitopes activate the immune system and cause inflammation in the small intestine, leading to symptoms like stomach pain, diarrhea, and fatigue. The only current treatment is a strict gluten-free diet.

However, avoiding gluten is challenging and costly. Even trace amounts can cause harm, and people often struggle with unintentional exposure. Because gluten is so important for the texture and structure of bread, completely removing it from wheat is not a practical solution for mass food production. Researchers have instead been exploring whether it’s possible to reduce or remove only the parts of gluten that are most harmful, while preserving its functional qualities for baking.

A Closer Look at Wheat Proteins and Their Role

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Wheat gluten is made up of two main protein groups: glutenins and gliadins. Glutenins help form the stretchy, elastic network that gives dough its strength. Gliadins contribute to the dough’s ability to expand. Gliadins are generally more problematic for people with celiac disease because they contain more of the immunogenic epitopes—the parts that trigger the immune reaction.

Of these, one particular group called alpha-gliadins stands out. They are not as critical for baking performance but are heavily loaded with the harmful sequences known to trigger strong immune responses in most people with celiac disease. These alpha-gliadins are encoded by three regions in the wheat genome, each located on a different version of chromosome 6: A, B, and D.

The Breakthrough: Targeted Deletions in Wheat Genes

In this study, researchers used a technique called gamma radiation to selectively delete sections of the wheat genome that include the genes for alpha-gliadins. They developed three versions of wheat with these deletions, each removing alpha-gliadins from one of the three chromosomes. The deletions were labeled Δgli-A2, Δgli-B2, and Δgli-D2, referring to the respective chromosomes affected.

Of the three, the Δgli-D2 deletion had the most dramatic effects:

• It removed a significant number of harmful epitopes, including some of the most potent ones known as the 17-mer and 33-mer sequences.
• It improved gluten strength and breadmaking quality.
• It did not harm the grain’s yield, protein content, or dough elasticity.

Interestingly, alpha-gliadins from chromosome 6D contain a unique structural feature—seven cysteine residues—that allow them to interact with the gluten network in a way that may actually weaken it. Removing these particular proteins seems to make the gluten network stronger, not weaker.

Breadmaking Without the Harmful Parts

The Δgli-D2 deletion led to stronger gluten and better baking performance. This was not expected, as removing parts of gluten could potentially weaken dough quality. However, it turns out that some alpha-gliadins may act like “chain terminators” in the gluten network, preventing it from growing stronger. Eliminating them allows the glutenins to form longer and more robust protein chains, leading to better dough properties.

Even more importantly, this genetic change removed around 81 percent of the most harmful gluten epitopes from the alpha-gliadin family. This could significantly reduce the risk that wheat consumption would trigger the immune response in people genetically at risk for celiac disease.

Combining Deletions for Bigger Impact

While Δgli-D2 had the most benefit, combining it with Δgli-A2 (removing alpha-gliadins from chromosome 6A) offered additional reduction in harmful epitopes, without compromising wheat quality. However, attempting to remove alpha-gliadins from all three chromosomes (adding Δgli-B2) led to sterile plants that could not reproduce. This limitation arises because wheat is a polyploid—meaning it has multiple sets of chromosomes—and deleting all versions of an important gene can lead to problems in plant development.

To further reduce the toxicity of wheat for people with celiac disease, scientists are also exploring deletions in other parts of the wheat genome that encode different kinds of gliadins, such as omega- and gamma-gliadins. Some promising results have been achieved using gene editing tools like CRISPR, which allows precise removal of these toxic segments without affecting other important traits.

Why This Study Matters

This research represents a significant step toward producing wheat that is safer for people at risk of celiac disease—without sacrificing the quality of the final baked product. Rather than attempting to eliminate gluten entirely, which would ruin bread’s texture and taste, the researchers have found a way to remove the most harmful components while maintaining and even improving the wheat’s baking performance.

Importantly, this modified wheat is publicly available and could be used by breeders and food companies to develop new varieties of bread and pasta that are lower in celiac-triggering proteins. While these products would still not be completely safe for people with celiac disease, they could help reduce the overall population burden of the condition by lowering the chances of triggering it in genetically susceptible individuals.

In the future, combining these deletions with other strategies—such as further CRISPR modifications or enzyme treatments—might make it possible to create wheat-based foods that are significantly less toxic, or even fully safe, for people with celiac disease.

Conclusion: A Promising Path Forward

The study shows that it is possible to selectively remove the most dangerous parts of wheat gluten while improving bread quality. By deleting specific genes for alpha-gliadins, particularly those on chromosome 6D, researchers have created a type of wheat that contains far fewer celiac-triggering components and performs better in baking. For individuals with celiac disease, this work opens the door to a future where wheat-based products may one day be safer to consume, reducing health risks and improving quality of life. Although more work is needed, especially to remove all problematic proteins, this study marks a promising advance in the quest to make wheat healthier for everyone.

Read more at: link.springer.com