| Summary: | Background: Non-celiac wheat sensitivity (NCWS) is a poorly understood gluten-related disorder (GRD) and its prominent symptoms can be ameliorated by gluten avoidance. This study aimed to determine the effectiveness of a probiotic mixture in hydrolyzing gliadin peptides (toxic components of gluten) and suppressing gliadin-induced inflammatory responses in Caco-2 cells. Methods: Wheat dough was fermented with a probiotic mix for 0, 2, 4, and 6 h. The effect of the probiotic mix on gliadin degradation was monitored by SDS-PAGE. The expression levels of IL-6, IL-17A, INF-γ, IL-10, and TGF-β were evaluated using ELISA and qRT-PCR methods. Results: According to our findings, fermenting wheat dough with a mix of <i>B. longum</i>, <i>L. acidophilus</i>, and <i>L. plantarum</i> for 6 h was effective in gliadin degradation. This process also reduced levels of IL-6 (<i>p</i> = 0.004), IL-17A (<i>p</i> = 0.004), and IFN-γ (<i>p</i> = 0.01) mRNA, as well as decreased IL-6 (<i>p</i> = 0.006) and IFN-γ (<i>p</i> = 0.0009) protein secretion. 4 h fermentation led to a significant decrease in IL-17A (<i>p</i> = 0.001) and IFN-γ (<i>p</i> = 0.003) mRNA, as well as reduced levels of IL-6 (<i>p</i> = 0.002) and IFN-γ (<i>p</i> < 0.0001) protein secretion. This process was also observed to increase the expression levels of IL-10 (<i>p</i> < 0.0001) and TGF-β (<i>p</i> < 0.0001) mRNA. Conclusions: 4 h fermentation of wheat flour with the proposed probiotic mix might be a good strategy to develop an affordable gluten-free wheat dough for NCWS and probably other GRD patients.
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