Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China; Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China; Milk and Milk Products Inspection Center of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China; State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China; Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China; Milk and Milk Products Inspection Center of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China; State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
Toxicon. 2020 Jun;180:49-61. doi: 10.1016/j.toxicon.2020.03.008. Epub 2020 Apr 5.
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 μg/mL) and OTA (4 μg/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.
受真菌毒素污染的牛奶可能会威胁到人类健康；因此，有必要展示牛奶中真菌毒素的毒理学效应。最近，研究人员越来越关注个别谷物污染真菌毒素（即玉米赤霉烯酮和脱氧雪腐镰刀菌烯醇）的免疫毒性作用。然而，关于黄曲霉毒素 M1（AFM1）的肠道免疫毒性，更不用说 AFM1 和赭曲霉毒素 A（OTA）的组合的信息了，而这两种毒素通常在牛奶中共存。为了揭示这些真菌毒素引起的炎症反应，分析了分化的 Caco-2 细胞中与炎症相关的基因的表达，结果表明 AFM1（4μg/mL）和 OTA（4μg/mL）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。跨组学分析确定了这种协同作用的几个机制：（i）与单独刺激任何一种化合物相比，联合使用导致参与免疫相关途径的蛋白质更强诱导；（ii）两种药物的联合作用针对同一途径的不同点；（iii）两种药物的联合作用激活了特定的炎症相关途径。这些结果表明，AFM1 和 OTA 的联合使用可能会加剧肠道炎症，这表明监管机构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。
