Beisl Julia, Varga Elisabeth, Braun Dominik, Warth Benedikt, Ehling-Schulz Monika, Del Favero Giorgia, Marko Doris
Department of Food Chemistry and Toxicology, University of Vienna, Währinger Straße 38, 1090 Vienna, Austria.
Institute of Microbiology, Department of Pathobiology, University of Veterinary Medicine, Veterinärplatz 1, 1210 Vienna, Austria.
Toxins (Basel). 2021 Mar 4;13(3):189. doi: 10.3390/toxins13030189.
The human intestine is regularly exposed to ingested food contaminants, such as fungal and bacterial toxins, which have been described to co-occur in a mixed diet. Thus, it is of utmost importance to understand possible interactions between contaminants of different origin. Hence, we investigated the single and combined effects of one of the most abundant mycotoxins, deoxynivalenol (DON; 0.1 to 10 µg/mL), and the bacterial toxin cereulide (CER; 1 to 100 ng/mL) on differentiated human Caco-2 (C2BBe1) cells cultured in a transwell system. We tested the capacity of the two toxins to alter the intestinal integrity and further investigated the uptake of both compounds and the formation of selected DON metabolites. CER alone (10 and 100 ng/mL) and in combination with DON (10 ng/mL CER with 1 µg/mL DON) was found to alter the barrier function by increasing the transepithelial electrical resistance and the expression of the tight junction protein claudin-4. For the first time, DON-3-sulfate was identified as a metabolite of human intestinal cells in vitro. Moreover, co-incubation of CER and DON led to an altered ratio between DON and DON-3-sulfate. Hence, we conclude that co-exposure to CER and DON may alter the intestinal barrier function and biotransformation of intestinal cells.
人类肠道经常接触摄入的食物污染物，如真菌毒素和细菌毒素，在混合饮食中已发现它们共同存在。因此，了解不同来源污染物之间可能的相互作用至关重要。为此，我们研究了最常见的霉菌毒素之一脱氧雪腐镰刀菌烯醇（DON；0.1至10μg/mL）和细菌毒素蜡样芽胞杆菌毒素（CER；1至100 ng/mL）对在transwell系统中培养的分化人Caco-2（C2BBe1）细胞的单一和联合作用。我们测试了这两种毒素改变肠道完整性的能力，并进一步研究了两种化合物的摄取以及选定的DON代谢物的形成。发现单独的CER（10和100 ng/mL）以及与DON联合使用（10 ng/mL CER与1μg/mL DON）通过增加跨上皮电阻和紧密连接蛋白claudin-4的表达来改变屏障功能。首次在体外将硫酸脱氧雪腐镰刀菌烯醇鉴定为人肠道细胞的代谢物。此外，CER和DON的共同孵育导致DON和硫酸脱氧雪腐镰刀菌烯醇之间的比例发生变化。因此，我们得出结论，同时接触CER和DON可能会改变肠道屏障功能和肠道细胞的生物转化。
