Cereals are infected by a range of biological and chemical contaminants, including fungi that may produce mycotoxins such as deoxynivalenol (DON) and HT-2 toxin, bacteria and protozoa. Humans ingesting cereals are therefore potentially exposed to a mixture of natural contaminants. DON is present in almost all cereal-based foodstuffs. Previous estimations of the dietary exposure in Norway indicate that some groups of the population may have an DON-intake close to or exceeding the Tolerable Daily Intake (TDI); and the levels in grains seem to increase. An improved estimate of the human exposure is therefore needed to ensure that present contamination levels are safe. Samples of human blood and urine from individuals with a known diet will be analysed for selected mycotoxins and their products from human metabolism. The project aims further to establish a national database on trichothecenes in food. The intake of trichothecenes will be estimated from both biomonitoring and food data, and major sources of trichothecenes in the diet identified. The estimated intake will then be compared with the TDIs.
The effects of DON and the sum of T-2 toxin and HT-2 toxins occurring at doses realistic for humans are feed refusal, gastrointestinal disturbances, impairment of the immune system and reduced formation of blood cells. Naturally infected grains are more toxic than feed with the corresponding levels of pure toxin, suggesting synergistic effects. Here we will explore the possible role of other biological agents, infections for mycotoxin-induced inflammatory effects in primary human immune cells. The effects of priming immune cells with various biological relevant components (receptor ligands) before exposure to selected Fusarium and Alternaria mycotoxins on cytokine production will be examined. The effects of the most interesting single contaminants and components will be examined deeper in a model simulating the interaction between the epithelial layer and immune cells will be explored in vitro, and the effects of defined mixtures will be characterised in the most sensitive model.
The detailed goals of the project are:
• Establish biomarkers of exposure to mycotoxins and apply these biomarkers to quantify human exposure
• Build a database on contents of trichothecenes in Norwegian food items
• Calculate/assess dietary intake of trichothecenes in selected population groups
• Study the effects of selected fungal secondary metabolites on various human immune cells directly and on cells primed with biological contaminants (relevant receptor ligands)
• Study the most relevant effects of fungal metabolites, and priming on a co-culture of gastrointestinal epithelial and immune-cells
• Study relevant mixtures in the most sensitive model
• Assess the significance of the findings to human health
This project is a collaboration between the Norwegian Veterinary Institute, the Institute of Public Health, the Norwegian University of Life Sciences and Michigane State University. Project leader is Gunnar S. Eriksen.
Micrographs of human macrophages exposed to alternariol (left) vs. control (right)