How Deamidation Changes Gliadin and Reduces Its Harm to the Intestine: A Study Summary for Patients and Families Living with Celiac Disease

Celiac.com 07/04/2025 - This study explored how a process called deamidation affects gliadin, a major component of gluten found in wheat. Gliadin is known to cause serious health issues for people with celiac disease or wheat allergies. The researchers wanted to find out if deamidation could make gliadin less harmful by changing how it behaves in the body after digestion.

More specifically, the study focused on how deamidated gliadin peptides (smaller protein pieces created during digestion) behave in terms of:

• How they cluster together (self-assembly)
• How they move through the protective mucus in the gut
• Whether they damage the cells that line the intestines

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The hope is that understanding these changes could lead to safer food products for people sensitive to gluten.

Why Gliadin Causes Problems in the Gut

Gliadin makes up 40–50 percent of wheat gluten and contributes to the stretchiness of dough. But for people with celiac disease or other wheat-related disorders, gliadin is a major trigger for inflammation and damage.

Here’s how it works:

1. After someone eats gluten, their digestive system breaks gliadin down into smaller pieces called peptides.
2. Some of these peptides are very sticky and able to form tiny particles that resemble surfactants, meaning they can interact with cell membranes.
3. These particles easily pass through the mucus barrier that normally protects intestinal cells.
4. Once they reach the surface of intestinal cells, the particles interact with cell membranes and may even damage or destroy them.

This damage allows the peptides to go deeper into the intestinal lining, where they can activate the immune system. This sets off the chronic inflammation seen in celiac disease.

What Is Deamidation and Why Might It Help?

Deamidation is a chemical process that changes specific parts of a protein. It converts certain neutral amino acids—like glutamine and asparagine—into acidic ones, such as glutamic acid or aspartic acid. This change introduces more negative electrical charges to the protein structure.

Researchers believe this process could:

• Make gliadin peptides less likely to form harmful clusters
• Reduce their ability to pass through mucus
• Limit their capacity to damage intestinal cells

Since gliadin contains a lot of glutamine, it’s especially susceptible to deamidation, which makes it a good candidate for modification.

In this study, researchers used citric acid—a safe and commonly available food acid—to gently deamidate gliadin and then investigated the effects.

How Deamidation Changed Gliadin Peptides

The research team treated gliadin with different levels of deamidation using citric acid. They then digested the proteins in the lab using enzymes similar to those found in the human stomach and intestines.

Here’s what they discovered:

1. Shorter, More Polar Peptides Were Formed

When gliadin was only slightly deamidated (less than 20 percent), the peptides that resulted after digestion were shorter and more polar, meaning they were more attracted to water. This made the peptide clusters smaller and more spherical in shape—less threatening to intestinal health.

2. Moderate Deamidation Changed the Shape and Size of Particles

At a moderate level of deamidation (around 26 percent), the peptides became more negatively charged. This changed the way they clumped together. Instead of forming round particles, they formed long, string-like shapes. These changes were driven by increased electrical interactions between the peptide molecules.

Improved Mucus Permeation, but Reduced Cell Damage

The study also looked at how easily these modified peptides could pass through a simulated mucus barrier, and whether they would harm intestinal cells (specifically Caco-2 cells, a model for human intestinal lining).

Key Findings:

• Mucus Penetration: Deamidated peptides moved through the mucus more efficiently due to their smaller or more flexible structures.
• Less Harm to Cells: Although the peptides could still pass through the mucus, they did not harm the intestinal cells the same way untreated gliadin peptides did. This was likely because the increased negative charge made them less likely to stick to and disrupt the cell membranes.

In untreated gliadin, positively charged regions (such as lysine and arginine) on the surface of the peptide clusters interact strongly with negatively charged components of cell membranes, causing damage. Deamidation weakens this attraction, reducing the peptides’ destructive potential.

How the Structural Changes Were Measured

To support their conclusions, the researchers used a variety of scientific tools to look at the gliadin peptides:

• SDS-PAGE to measure protein size
• FT-IR and fluorescence spectroscopy to examine protein folding
• Transmission electron microscopy to visualize particle shape
• HPLC-MS/MS to identify peptide sequences
• Cell culture studies to measure how peptides affected living intestinal cells

These techniques confirmed that deamidation not only changed the structure of the gliadin proteins but also their behavior in the digestive system.

Why This Matters for People with Celiac Disease

This study is important because it suggests a way to reduce the harm caused by gluten proteins without removing them completely. While avoiding gluten is the only treatment for celiac disease right now, this research points toward safer food processing methods that could one day lessen the risk of accidental gluten exposure.

By modifying gliadin through deamidation:

• The resulting peptides may be less likely to damage the gut lining.
• This could mean fewer immune triggers for people with gluten sensitivity or celiac disease.
• Food products made from deamidated gluten might be more tolerable in the future, though much more research is needed before this becomes a real-world option.

Conclusion: A Step Toward Safer Gluten for Sensitive Individuals

The researchers successfully demonstrated that deamidation changes the way gliadin peptides behave after digestion. These changes—especially shorter peptide length, altered particle shape, and reduced interaction with intestinal cells—help make the peptides less harmful. The findings support the potential for deamidation to be used as a food processing method to reduce gluten-related damage.

While this study was conducted in a lab and more clinical testing is needed, it opens a promising door for creating safer wheat-based products for people with celiac disease or gluten sensitivity.

Read more: sciencedirect.com