Microbial Transglutaminase Increases Uptake and Translocation of Gliadin Peptides in the Human Intestinal Epithelium.

Transglutaminase 2 (TG2) plays an essential role in the pathogenesis of celiac disease (CD) by modifying gliadin peptides. Additionally, microbial transglutaminase (mTG) was implicated in CD pathogenesis since it modifies gliadin peptides in the same way. mTG is used as a technical aid in the production of food items and might also be released by the intestinal microbiota. We aimed to characterize the interaction of mTG with different gliadin peptides and its effect on the epithelial and mucosal transport.We compared mTG- and TG2-mediated crosslinking of gliadin peptides using indirect enzyme-linked immunosorbent assay (ELISA) and immunoblot. Epithelial uptake of gliadin peptides P56-88 and P31-49 by Caco-2 cells and human duodenal biopsies was quantified by fluorometry and immunofluorescence microscopy. mTG had a much higher affinity towards different gliadin peptides than TG2. mTG significantly increased the uptake of gliadin peptide P56-88 and P31-49 by Caco-2 cells by nearly 10 times. Finally, mTG increased the uptake and colocalized with gliadin peptide P56-88 in the human duodenal mucosa. DmTG-mediated enzymatic modification of gliadin peptides is evident and influences the epithelial uptake of potentially detrimental gliadin peptides. The uncritical use of mTG in food production might therefore pose a potential threat for consumers.