Butyrate-Dependent Conformational Switch Promotes Nuclear Translocation of the Mustard Allergen Sin a 1 in Human Gut...

Sin a 1, the major allergen from mustard seeds, is a highly stable 2S albumin capable of reaching the intestinal epithelium in its intact form. In this study, we investigated whether butyrate, a microbiota-derived short-chain fatty acid, directly interacts with Sin a 1 and modulates its cellular behavior in Caco-2 cells. Circular dichroism analyses revealed that short-chain fatty acids induce conformational changes in Sin a 1. However, fluorescence spectroscopy showed that only butyrate modified the tertiary structure of the light chain, exposing a putative nuclear localization signal and thereby promoting the importin-dependent nuclear translocation of the allergen. In the absence of butyrate, Sin a 1 remained predominantly in the cytoplasm. In addition, butyrate altered NFKB1 transcriptional responses in Sin a 1-treated cells. Our findings reveal an effect of butyrate on the intracellular trafficking of allergens that had not previously been described, suggesting a novel mechanism by which microbiota-derived metabolites may influence food allergenicity.