Today is International Celiac Day. Celiac disease is a long-term autoimmune disorder that affects about one percent of the global population. It is caused by consuming gluten proteins found in wheat, barley, rye, and some oats. Following a gluten-free diet helps celiac patients avoid serious damage to their intestines. Along with colleagYes, Dr. Veronica Dodero, a chemist from Bielefeld University, has found new information about how certain molecules derived from gluten can cause leaky gut syndrome in people with celiac disease.
The main discovery of the study is that a specific protein fragment that forms in active celiac disease creates small structures called oligomers, which accumulate in a model of gut epithelial cells. The molecule’s technical name is 33-mer deamidated gliadin peptide (DGP). The research team has now learned that the presence of DGP oligomers can cause the gut lining to become leaky. The study has been published.The journal ‘Angewandte Chemie’ has published a study on Wheat Peptides Causing Leaky Gut. When we consume wheat, our bodies struggle to fully break down gluten proteins, which can result in the creation of large gluten fragments, also known as peptides, in our gut. In cases of active coeliac disease, researchers found that the enzyme tissue transglutaminase 2 (tTG2) in humans modifies a specific gluten peptide, leading to the formation of the 33-mer DGP. This typically occurs in a part of our gut called the lamina propria, but recent research has indicated that this process can also take place in the gut lining.The research team, consisting of members from different disciplines, used advanced microscopy and biophysical methods to study the formation of 33-mer DGP oligomers. Dr. Maria Georgina Herrera, the lead author of the study and a researcher at the University of Buenos Aires in Argentina, revealed that the accumulation of DGP in a gut cell model resulted in increased permeability. This discovery suggests that a weakened intestinal barrier may lead to leaky gut syndrome, where the intestine lining becomes permeable, allowing harmful substances to enter the bloodstream and causing inflammatory responses and various diseases.In celiac disease, there is ongoing discussion about the initial phases of increased permeability. The prevailing belief is that persistent inflammation in celiac disease results in a permeable gut. However, an alternative theory suggests that the primary cause is the impact of gluten on the cells of the gut lining. According to this perspective, gluten directly harms the cells of the intestinal lining, causing them to become permeable, which then leads to chronic inflammation and potentially contributes to the development of celiac disease in susceptible individuals.
Considering that gluten is consumed on a daily basis, the question arises: What molecular triggers are responsible for the leaky gut in celiac disease patients?? When 33-merDGP oligomers form, they have the potential to cause harm to the epithelial cell network. This can result in the passage of gluten peptides, bacteria, and other toxins into the bloodstream, leading to inflammation and potentially triggering autoimmunity in celiac disease.
The lead author of the study, Dr. Veronica Dodero from the Bielefeld Faculty of Chemistry, states that “Our findings support the medical hypothesis that damage to the epithelial barrier caused by gluten peptides is a contributing factor to the immune response in celiac patients, rather than being a consequence of it.”
The Link Between 33-mer DGP and Celiac Disease
Human leukocyte antigens (HLAs) areProteins located on the surface of the body’s cells are essential for the immune system to differentiate between the body’s own cells and foreign substances. In the case of celiac disease, two specific HLA proteins, HLA-DQ2 and HLA-DQ8, are closely linked to the condition. The 33-mer DGP perfectly fits with HLA-DQ2 or HLA-DQ8 and causes an immune response, leading to inflammation and damage to the small intestine. This strong interaction turns the DGP into what scientists refer to as a superantigen. For those affected, a gluten-free diet is the only lifelong treatment.Â
