The Effects of Mycotoxins on Pregnancy and Immune Development: (A Preclinical approach)

Mycotoxins are among the most important and highly prevalent nutritional contaminants worldwide. They are naturally produced as secondary metabolites of different fungal species, which can contaminate a wide range of agricultural products, especially cereal and grain-based food. Fusarium species are amongst the most prevalent fungal contaminants of grains, and produce the two most important classes of mycotoxins, trichothecenes (including deoxynivalenol (DON), T-2 toxin and HT-2 toxin) and zearalenones (ZEN). In humans and animals, exposure to Fusarium mycotoxins is associated with mutagenic, teratogenic, estrogenic, hemorrhagic, neurotoxic, hepatotoxic, and immunotoxic effects. Considering the widespread occurrence of these food contaminants and inevitable human exposure, this thesis aimed to investigate the adverse effects of exposure to commonly occurring Fusarium mycotoxins and potential mechanisms involved, with a special focus on DON, as this is the most prevalently occurring food contaminant worldwide. In this thesis, we showed that exposure to the major Fusarium mycotoxin DON, can adversely affect innate and adaptive immune responses, placental barrier, fetal survival and development. We further demonstrated that consuming DON-contaminated diets during pregnancy and lactation, induces long-term effects on the developing immune system of the offspring and shifts the balance in immune cell populations, hence increasing the susceptibility to allergic reactions and reducing immune responses to vaccination in later stages of life. Some specific non-digestible oligosaccharides (NDOs) have prebiotic and immune- modulating properties comparable to those observed for certain human milk oligosaccharides (HMOs). Specific structures of NDOs and HMOs are confirmed to have positive effects on improving adaptive immune responses. In this thesis we showed that nutritional supplementation with a specific NDO mixture rich in 3’-GL, can be beneficial in preventing or neutralising the adverse effects of DON on immune system. Thus, NDOs might be a suitable candidate as a supplement in infant formulae for boosting the immune system and preventing the harmful effects of early-life exposure to DON on the intestinal and immune systems.