Oral Exposure to <i>Clostridium difficile</i> Toxin A Aggravates Food Allergy by Intestinal Barrier Destruction, Mast Cell Activation, and Th2-Biased Immune Responses

Food allergy is a complex disease, with multiple environmental factors involved. Considering the regulatory effect of <i>Clostridium difficile</i> toxin A (Tcd A) on biological processes of allergic reactions, the role of oral exposure to Tcd A on food allergy was investigated. The intestinal permeability and β-hexosaminidase were promoted by Tcd A using the in vitro Caco-2 and HT-29 cells coculture monolayer and bone marrow-derived mast cell (MCs) degranulation model. When the sensitized mice were challenged with OVA and 4 μg of Tcd A, specific IgE and MCPT-1 levels were increased. The results of flow cytometry and ELISA demonstrated that the Th1 and Treg cells were reduced and higher IL-5 was induced. The jejunum staining showed that villus injury and MC accumulation were aggravated. All of the findings demonstrated that Tcd A could aggravate food allergy, and the orally exposed risk factors aggravating food allergy warrant increasing attention.