Transcriptomic and proteomic profiling reveals the intestinal immunotoxicity induced by aflatoxin M1 and ochratoxin A
Transcriptomic and proteomic profiling reveals the intestinal immunotoxicity induced by aflatoxin M1 and ochratoxin A
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DOI：
10.1016/j.toxicon.2020.03.008
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发表时间：
2020-06-01
期刊：
影响因子：
2.8
通讯作者：
Zheng, Nan
中科院分区：
文献类型：
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作者：
Gao, Yanan;Ye, Qiaoyan;Zheng, Nan
霉菌毒素污染的牛奶可能威胁人体健康；因此，有必要对牛奶中真菌毒素的毒理学效应进行研究。最近，研究人员更多地关注了单个谷物污染真菌毒素的免疫毒性作用，即玉米赤霉烯酮和脱氧雪腐烯醇。然而，关于黄曲霉毒素M1 （AFM1）的肠道免疫毒性的信息很少，更不用说AFM1和赭曲霉毒素a （OTA）的联合免疫毒性了，这两种毒素经常同时出现在牛奶中。为了揭示这些真菌毒素引起的炎症反应，我们分析了分化的Caco-2细胞中炎症相关基因的表达，表明AFM1 （4 μ g/mL）和OTA （4 μ g/mL）的混合物具有协同作用。还进行了综合转录组学和蛋白质组学分析。交叉组学分析确定了这种协同作用的几种机制：(i)与单独使用任何一种化合物相比，联合使用可以更强地诱导参与免疫相关途径的蛋白质；（ii）两种药物联合针对同一途径中的不同点；（iii）两种药物联合激活特异性炎症相关通路。这些结果提示AFM1和OTA联合使用可能会加重肠道炎症，提示监管部门在进行风险评估时应更加关注多种真菌毒素对食品的污染。
Mycotoxins-contaminated milk could threaten human health; therefore, it is necessary to demonstrate the toxicological effect of mycotoxins in milk. Most recently, researchers have paid more attention to the immunotoxic effects of the individual cereal-contaminating mycotoxins, namely, zearalenone and deoxynivalenol. However, there is scant information about the intestinal immunotoxicity of aflatoxin M1 (AFM1), let alone that of a combination of AFM1 and ochratoxin A (OTA), which often co-occur in milk. To reveal the inflammatory response caused by these mycotoxins, expression of inflammation-related genes in differentiated Caco-2 cells was analyzed, demonstrating a synergistic effect of the mixture of AFM1 (4 mu g/mL) and OTA (4 mu g/mL). Integrative transcriptomic and proteomic analyses were also performed. A cross-omics analysis identified several mechanisms underlying this synergy: (i) compared with stimulation with either compound alone, combined use resulted in stronger induction of proteins involved in immunity-related pathways; (ii) combination of the two agents targeted different points in the same pathways; and (iii) combination of the two agents activated specific inflammation-related pathways. These results suggested that combined use of AFM1 and OTA might exacerbate intestinal inflammation, indicating that regulatory authorities should pay more attention to food contamination by multiple mycotoxins when performing risk assessments.