Detoxification Mechanism and the Impact of Transamidation-Modified Gliadin on Celiac-Based Gluten Sensitivity: The Potential of Unlocking Gluten Tolerance in Functional Food

Transamidation of gliadin under reducing conditions has shown promise in mitigating celiac disease-related gluten toxicity. However, comprehensive evaluation in both <i>in vitro</i> and <i>in vivo</i> models is crucial. This study investigated the effects of transamidated gliadin (GM) on celiac toxicity using Caco-2 cell monolayers, bone marrow-derived dendritic cells (BMDCs), and a BALB/c mouse model. In cellular level, GM mitigated intestinal damage compared to unmodified gliadin and stimulated a less pronounced pro-inflammatory response, suggesting a reduced activation of the T-cell-mediated immune system. <i>In vivo</i>, the GM group displayed lower levels of pro-inflammatory factors and less pronounced Th1/Th2 imbalance compared to the unmodified gliadin group. Notably, the GM also improved the balance of the intestinal microbiome. In brief, GM exhibited significantly reduced celiac toxicity in both cellular and animal models that mimics the intestinal environment of celiac disease. These findings suggest that transamidation treatment holds potential as a safer alternative strategy to lower the toxicity of wheat gliadin/wheat flour, potentially paving the way for developing modified gluten-based foods with desirable texture or ingredients as a nutritional enhancer or structure improver, benefiting individuals with specific needs.