Impact of early life exposure to the mycotoxin DON on the development of food allergy

Background: Early life exposure to detrimental compounds can have significant effects on development. Previously we showed that the trichothecene deoxynivalenol (DON), a fungal metabolite found in grain-based human diets, acts as a specific disruptor of the intestinal tight junction network and hence might contribute to gastrointestinal disorders. We hypothesized that the developing fetus and/or newborn would be exposed to DON through the placenta and breastmilk, resulting in a negative impact on gastro-intestinal development, thereby increasing susceptibility to develop gastrointestinal disorders such as food allergies. Method: Upon arrival, C3H/HeOuJ mice were fed the control AIN93G diet and breeding pairs were formed. Upon assessment of a sperm plug, females were either kept on the control diet or a control diet containing 10 mg DON/kg feed, until 15 days after delivery of the pups. The offspring of the control and the DON-treated dams were divided into 1 sham-group, 2 oral tolerance-group and 3 food allergy group. Mice in group 1 were given oral gavages with PBS, mice in group 2 received PBS with 40 mg/ml OVA and group 3 was given 40 mg/ml OVA and 20 μg/ml Cholera toxin (CT). After weaning, offspring were were sensitized orally with OVA + CT. Acute allergic skin responses, shock symptoms, and specific plasma immunoglobulins were measured upon intradermal ovalbumin challenge. T cell populations were analyzed with use of flow cytometric analysis in spleen and mesenteric lymph nodes (MLN). Results: Increased intestinal permeability in the dams as a result of DON exposure was observed by increased translocation of FITC dextran across the intestinal interfaces. However, maternal exposure to DON did not affect acute allergic skin responses or shock symptoms in the offspring. Flow cytometric analysis of the MLN and the spleen revealed no clear effect of maternal DON exposure on the effector responses in the offspring. OVAspecific and total immunoglobulin levels were similar between offspring of control dams and DON-treated dams. Conclusion: Our study suggests that maternal DON exposure in the current experimental setup does not affect the outcome of the OVA-specific food allergy in the offspring. It is possible that the DON-content of the diet was not sufficient to affect immune development in the offspring. Current research focuses on early life exposure of the developing fetus and/or newborn to different detrimental compounds in the maternal diet.