What is it about?

Gliadin is a protein present in wheat gluten that is not fully degraded during human digestion. The remaining large undigested peptides produce diverse diseases affecting around 5% of the general population. In general, the complicated relationship between food properties, behavior during digestion, and their contribution to human nutrition and health are not well understood. Here, we present the first evaluation of pepsin gliadin digest (p-gliadin) using a physicochemical approach combined with a screening panel of inflammatory biomarkers related to Celiac Disease (CeD) in the Caco-2 cell line. We found that the p-gliadin system behaves as a self-organized solution composed of oligomers and fibrils, which triggers the up-regulation of the mRNA of pro-apoptotic, chemoattractive, inflammatory, and permeability CeD related genes in the Caco-2 cell line.

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Why is it important?

Our findings led us to suggest that p-gliadin peptide supramolecular structures' interaction with the epithelial barrier could be responsible for the early tissue inflammatory response observed in CeD. In conclusion, it is revealed p-gliadin supramolecular structures' pathological role in the human epithelial cellular model, opening avenues to nutritional or therapeutic strategies to modulate the observed aggregation process.


Pasta, bread, biscuits: supermarkets are stocking ever more gluten-free versions of their products. For people who suffer from coeliac disease or non-coeliac gluten sensitivity (NCGS), this is very practical because, in their case, products that contain gluten cause symptoms that can range from diarrhea to infertility and colon cancer. But should healthy people also go for gluten-free pizza? What is gluten anyway, and why can it be so dangerous? This is precisely the point where our research kicks in – with the aim of gaining greater insights into gluten tolerance. Gluten is a complex mixture of proteins found in cereals like wheat, barley and rye. The main problem is that gluten proteins are not completely broken down in the human body, so large gluten fragments circulate the organism and are expelled in urine. However, some people’s bodies detect gluten fragments as a sign of alarm activating their immune system and lead to inflammation and disease. Once this response occurs, those affected must avoid eating gluten for the rest of their lives. Together with my collaborators, we had proved that undigested gluten fragments form structures like tiny building blocks similar to those formed in Alzheimer's disease and Huntington's disease. These building blocks produce toxic super-structures which possibly have a decisive impact on a person’s state of health. I think these results will help to answer some of the important questions surrounding gluten intolerance and human nutrition. ■

Veronica Dodero
Universitat Bielefeld

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This page is a summary of: Pepsin Digest of Gliadin Forms Spontaneously Amyloid‐Like Nanostructures Influencing the Expression of Selected Pro‐Inflammatory, Chemoattractant, and Apoptotic Genes in Caco‐2 Cells: Implications for Gluten‐Related Disorders, Molecular Nutrition & Food Research, June 2021, Wiley, DOI: 10.1002/mnfr.202100200.
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