The intestinal barrier as an emerging target in the toxicological assessment of mycotoxins

Abstract

Mycotoxins, the secondary metabolites of fungal species, are the most frequently occurring natural food contaminants in human and animal diets. Risk assessment of mycotoxins focused as yet on their mutagenic, genotoxic and potential carcinogenic effects. Recently, there is an increasing awareness of the adverse effects of various mycotoxins on vulnerable structures in the intestines. In particular, an impairment of the barrier function of the epithelial lining cells and the sealing tight junction proteins has been noted, as this could result in an increased translocation of luminal antigens and pathogens and an excessive activation of the immune system. The current review aims to provide a summary of the available evidence regarding direct effects of various mycotoxins on the intestinal epithelial barrier. Available data, based on different cellular and animal studies, show that food-associated exposure to certain mycotoxins, especially trichothecenes and patulin, affects the intestinal barrier integrity and can result in an increased translocation of harmful stressors. It is therefore hypothesized that human exposure to certain mycotoxins, particularly deoxynivalenol, as the major trichothecene, may play an important role in etiology of various chronic intestinal inflammatory diseases, such as inflammatory bowel disease, and in the prevalence of food allergies, particularly in children.

Keywords: Intestinal permeability; Mucosal inflammation; Mycotoxins; Tight junction proteins.

Fig. 1

Schematic illustration of the mycotoxin-induced intestinal epithelial barrier breakdown. The gut mucosa is constantly challenged by a diverse microbial community (, ), food-borne toxins (T) and foreign antigens (). The most prominent examples of food-borne toxins primarily associated with an impairment of the intestinal barrier are mycotoxins. Various mycotoxins have been shown to induce intestinal barrier breakdown demonstrated by a decrease in TEER, an increase in paracellular transport and changes in the expression as well as distribution pattern of different TJ proteins. The data shown in the figure have been demonstrated by in vitro studies unless otherwise stated (*in vivo studies, **in vitro as well as in vivo studies). Abbreviations used: 3-Ac-DON 3-acetyl deoxynivalenol, 15-Ac-DON 15-acetyl deoxynivalenol, AFB ₁ aflatoxin B₁, AFM ₁ aflatoxin M₁, α-ZOL alpha-zearalenol, β-ZOL beta-zearalenol, CLDNs claudins, DON deoxynivalenol, E. coli Escherichia coli, FB ₁ fumonisin B₁, FITC-dextran fluorescein isothiocyanate-dextran, HRP horseradish peroxidase, LY lucifer yellow, M. tuberculosiss Mycobacterium tuberculosiss, ND not determined, OCLN occludin, OTA ochratoxin A, PAT patulin, S. typhimurium Salmonella typhimurium, TEER transepithelial electrical resistance, TJ tight junction, ZOs zonula occludens