In vitro and in vivo studies of individual and combined effects of fusarium toxins on the intestinal immunity : a risk assessment and potential target for probiotic intervention

The most important Fusarium toxins that may potentially affect human and animals’ health are trichothecenes such as nivalenol (NIV), deoxynivalenol (DON), zearalenone (ZEA) and fumonisin B1 (FB1). Combined effects of Fusarium toxins are of great concerns because of their wide co-occurrence in foodstuff. Investigations on the combined effects of these mycotoxins are scarce and only few studies have been reported previously using endpoints that include inhibition of protein and DNA syntheses, DNA methylation and fragmentation, cell viability and proliferation. Yet, the combined effects of mycotoxins on the intestinal immunological defense mechanisms are poorly understood. In recent years, there has been an increasing interest in using probiotic bacteria in inhibiting the absorption of mycotoxins from consumed food in the gastrointestinal (GI) tract. In this research project, the effects of individual and mixtures of Fusarium toxins, DON, NIV, ZEA and FB1 on the immunomodulation of antimicrobial peptides, cytokines and mucus production in the intestinal epithelial cells (IECs) were first investigated in vitro. In vivo experiments were also conducted to mimic conditions inside the intestinal tract to evaluate the potential protective capacity of probiotic bacteria to interfere with the adverse effects of Fusarium toxins. In vitro studies clearly demonstrated the ability of DON, NIV, ZEA and FB1 to differentially modulate the synthesis and secretion antimicrobial peptides, proinflammatory cytokines and secretory mucins. When mycotoxin combinations were assessed, toxicity effects were shown to be additive in most of the toxin mixtures, though non-additive interactions were observed in some of the mixtures. In vivo studies have shown that chronic ingestion of DON/ZEA mix induced histological changes, reduced tight junction protein gene expression, and modulated plasma cytokine and serum immunoglobulin (Ig) levels. Supplementation of Lactobacillus rhamnosus strain GG (LGG) before and after DON/ZEA exposure in mice can improve, in certain extent, the intestinal barrier functions, as shown by increased tight junction protein expression, regulation of goblet cell mucus secretion, improvement of the local intestinal immune function as well as inhibition of inflammatory responses in the intestine. These changes may be associated with changes in gut microbiota composition. In summary, these results show that DON, NIV, ZEA and FB1 expressed different responses on intestinal immunological defence mechanism through the modulation of antimicrobial peptides, cytokines and mucus synthesis, which are of significant relevance to the risk assessment process. LGG can beneficially modulate the mycotoxin-compromised enterocytes-mediated defense responses by reducing inflammatory atmosphere, enhancement of intestinal barrier and alteration of the gut microbiota. Future studies for the properties and mechanism of probiotics as means of mycotoxin intervention will be warranted. These will provide a greater understanding of potential novel nutritional modalities to reduce exposure to Fusarium toxins and their combinations.published_or_final_versionBiological SciencesDoctoralDoctor of Philosoph