Study identifies key gluten peptides that cause leaky gut in celiac disease patients

Today is International Celiac Disease Day. Celiac disease is a chronic autoimmune disease that occurs in approximately 1% of the world's population. This is caused by ingesting gluten proteins from wheat, barley, rye, and some oats. A gluten-free diet protects people with celiac disease from severe intestinal damage. Chemist Dr. Veronica Dodero from Bielefeld University, in collaboration with her colleagues, was able to uncover new details about how certain gluten-derived molecules cause leaky gut syndrome in celiac disease.

A key finding of this study is that specific protein fragments formed in active celiac disease form nanosized structures, so-called oligomers, that accumulate in an intestinal epithelial cell model. The technical name of this molecule is 33-mer deamidated gliadin peptide (DGP). The research team has now discovered that the presence of DGP oligomers can cause the tightly closed intestinal lining to open, causing leaky gut syndrome.This research is now published in the journal “Applied Chemistry”.

Wheat peptides that cause leaky gut

When we eat wheat, our bodies are unable to fully break down gluten proteins. This can lead to the formation of large gluten fragments (peptides) in your intestines. Researchers found that in active celiac disease, the enzyme tissue transglutaminase 2 (tTG2) present in humans modifies certain gluten peptides, resulting in the formation of the 33-mer His DGP. did. This usually occurs in a part of the intestine called the lamina propria. However, recent studies have shown that this process can also occur in the intestinal lining.

“Our interdisciplinary team characterized the formation of 33-mer DGP oligomers through high-resolution microscopy and biophysical techniques. She is a researcher at the University of Buenos Aires in Argentina and a postdoctoral fellow at Bielefeld.

When the intestinal barrier is weakened

Leaky gut syndrome occurs when the lining of the intestines becomes permeable, allowing harmful substances to enter the bloodstream, causing inflammatory reactions and various diseases. In celiac disease, there is debate about the early stages of increased permeability. Mainstream theory suggests that chronic inflammation in celiac disease causes leaky gut. However, there is a second theory of his that claims that gluten's effect on the intestinal lining cells is the main culprit. In this view, gluten directly damages cells in the intestinal lining, making them permeable and causing chronic inflammation, potentially leading to people being more susceptible to celiac disease.

But gluten is consumed every day, so what are the molecular factors that cause leaky gut in celiac patients? When 33-merDGP oligomers form, they damage the epithelial cell network and cause gluten peptides, bacteria, and other Too many toxins enter the bloodstream, causing inflammation and, in celiac disease, can lead to autoimmunity.

“Our findings support the medical hypothesis that epithelial barrier impairment promoted by gluten peptides is a cause, rather than a consequence, of the immune response in patients with celiac disease,” said the study's first author. says Dr. Veronica Dodero from the Bielefeld Department of Chemistry. .

Relationship between 33-mer DGP and celiac disease

Human leukocyte antigens (HLA) are proteins found on the surface of cells in the body. They play an important role in the immune system by helping the immune system distinguish between self (the body's own cells) and non-self (foreign substances such as bacteria and viruses). In celiac disease, two specific HLA proteins are strongly associated with this condition: HLA-DQ2 and HLA-DQ8. 33-mer DGP is fully compatible with HLA-DQ2 or HLA-DQ8 and triggers an immune response, leading to inflammation and small intestinal villous atrophy. This strong interaction turns DGP into what scientists call a superantigen. For those affected, a gluten-free diet is the only lifelong treatment.

“Applied chemistry”

This publication is one of the most famous magazines in the field of chemistry. Published by the German Chemical Society. According to Clarivate Data Services, this journal has an impact factor of 16.6 (2022). This makes it one of the most influential publications in the field.