Exposure and effect of mycotoxin mixtures in infants

Molds produce a wide variety of metabolites, of which some, the so-called mycotoxins, can be highly toxic to humans and animals. Many of these fungal toxins are ingested through the diet and can cause adverse health effects. The effects of these food contaminants on human health depend on their toxicological properties and actual exposure levels. Moreover, the metabolism, break down and excretion of toxins plays an important role. Therefore, the X-eff project will investigate typical exposure patterns and the metabolic effects caused by chronic low-dose exposures. State-of-the-art analytical instruments will be used to develop mass spectrometry-based methods that can be used to determine a vast number of mycotoxins at extremely low concentrations in blood, feces, urine, and breast milk. These new methods will allow for the accurate quantitation of mycotoxin burden of an individual or a specific population. The newly established methods will subsequently be applied in epidemiological studies to study maternal and neonatal exposure in detail. For this purpose, samples from each a clinic each in Vienna and the USA will be tested to investigate possible country-specific differences in the contamination patterns. New findings on average and maximum exposures as well as the human detoxification potential will be generated in the context of these studies. Furthermore, we will apply innovative metabolomic and exposomic technology to elucidate how the toxins alone and in combination influence the endogenous human metabolism in a cell model. For the first time, actual toxin concentrations and combinations that were identified as characteristic in the tested individuals will be tested in this proof-of-principle experiments. In the long term, the aim of the X-eff project is to significantly reduce the exposure of infants to these naturally occurring food contaminants and to investigate whether specific diseases may be associated with low but chronic mycotoxin levels. The project results will also contribute to a deeper understanding of the molecular effects of mycotoxin mixtures in the context of the exposome paradigm.

Mycotoxins are toxic compounds naturally produced by moulds in foods such as cereals and nuts. Exposure to mycotoxins can adversely influence human health and potentially play pivotal roles in diseases such as liver cancer. Thus, human biomonitoring of mycotoxins using ultra-sensitive liquid chromatography tandem mass spectrometric (LC-MS/MS) based assays is crucial for accurate exposure assessment in population-based studies. In this project, ultra-sensitive LC-MS/MS based assays were developed and validated for human breast milk, urine, stool, serum and plasma. These novel analytical assays were applied to assess mycotoxin exposure in different cohorts including extremely premature infants and their mothers from Vienna, Austria and pregnant mothers from the USA. For generating even more comprehensive regional data, the innovative technologies were additionally applied to biological samples from cohorts in Spain and Nigeria. Mycotoxin exposure was evident in the studied cohorts irrespective of the type of population. All the extremely premature infants were exposed to ochratoxin A while, nearly half of the US cohort exceeded the established human biomonitoring guidance value (HBM-GV) for urinary deoxynivalenol. Overall, this project yielded more comprehensive exposure data which will be a solid foundation for future intervention strategies to reduce potentially negative effects in newborns.