Oral co-exposure to Clostridioides difficile toxin A and ovalbumin disrupts intestinal homeostasis and predisposes to food allergy in mice.

Clostridioides difficile toxin A (TcdA) has been identified as an orally exposed risk factor of food allergy during the challenge phase in our previous study, however, its role in the sensitization remains unclear. To comprehensively investigate the potential role of TcdA (0.5 μg or 4 μg) in allergic sensitization, this study constructed two mouse models: a short-term orally co-exposed OVA and TcdA model, and a TcdA-induced OVA-oral sensitization model. An oral co-exposure model was firstly established to evaluate the effects of TcdA on intestinal homeostasis. ZO-1 and occluding expressions were decreased with the co-exposure of ovalbumin (OVA) and 4 μg TcdA. Concurrently, beta diversity of the microbiota was diminished, and the intestinal immune response was dysregulated. Furthermore, typical allergic indicators, including OVA-specific IgE and MCPT-1, remained unchanged following the application of TcdA during the sensitization phase. However, the higher IL-4, lower IFN-γ and TGF-β were induced. These results indicate that TcdA could disrupt intestinal homeostasis and subsequently predispose to allergen sensitization.