Deoxynivalenol (DON), one of the most abundant mycotoxins in cereal products, was recently detected with other mycotoxins and the emetic bacterial toxin cereulide (CER) in maize porridge. Within a cereal-based diet, co-exposure to these toxins is likely, hence raising the question of combinatory toxicological effects. While the toxicological evaluation of DON has quite progressed, consequences of chronic, low-dose CER exposure are still insufficiently explored. Information about the combinatory toxicological effects of these toxins is lacking. In the present study, we investigated how CER (0.1-100 ng/mL) and DON (0.01-10 µg/mL) alone and in a constant ratio of 1:100 (CER:DON) affect the cytotoxicity and immune response of differentiated human intestinal Caco-2 cells. While DON alone reduced cell viability only in the highest concentration (10 µg/mL), CER caused severe cytotoxicity upon prolonged incubation (starting from 10 ng/mL after 24 h and 48 h, 2.5 ng/mL and higher after 72 h). After 72 h, synergistic effects were observed at 2.5 ng/mL CER and 0.25 µg/mL DON. Different endpoints of inflammation were investigated in interleukin-1β-stimulated Caco-2 cells. Notably, DON-induced interleukin-8 transcription and secretion were diminished by the presence of 10 and 25 ng/mL CER after short-term (5 h) incubation, indicating immunosuppressive properties. We hypothesise that habitual consumption of cereal-based foods co-contaminated with CER and DON may cause synergistic cytotoxic effects and an altered immune response in the human intestine. Therefore, further research concerning effects of co-occurring bacterial toxins and mycotoxins on the impairment of intestinal barrier integrity, intestinal inflammation and the promotion of malnutrition is needed.

中文翻译：

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蜡菊酯和脱氧雪腐烯酚对人Caco-2细胞体外存活率和炎症的联合作用。

谷类产品中最丰富的霉菌毒素之一，脱氧雪腐烯醇（DON）最近在玉米粥中与其他霉菌毒素和催吐细菌毒素cereulide（CER）一起被检测到。在谷物饮食中，可能会同时暴露于这些毒素，因此引发了组合毒理学效应的问题。尽管DON的毒理学评估取得了很大进展，但仍未充分探讨慢性低剂量CER暴露的后果。缺乏有关这些毒素的组合毒理作用的信息。在本研究中，我们研究了CER（0.1-100 ng / mL）和DON（0.01-10 µg / mL）并以1：100的恒定比率（CER：DON）如何影响分化的细胞毒性和免疫反应人肠中的Caco-2细胞。单独的DON仅在最高浓度（10 µg / mL）时会降低细胞活力，而CER在长时间孵育后会引起严重的细胞毒性（24小时和48小时后从10 ng / mL开始，在72小时后从2.5 ng / mL开始升高）。72小时后，在2.5 ng / mL CER和0.25μg/ mL DON下观察到协同作用。在白介素1β刺激的Caco-2细胞中研究了炎症的不同终点。值得注意的是，在短期（5 h）孵育后，通过10和25 ng / mL CER的存在，DON诱导的白介素8转录和分泌减少，表明具有免疫抑制特性。我们假设习惯性食用与CER和DON共同污染的谷类食品可能会导致协同的细胞毒性作用，并改变人体肠道的免疫反应。因此，