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; Institute of Food Science and Technology, 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.
Ecotoxicol Environ Saf. 2024 Jun 15;278:116336. doi: 10.1016/j.ecoenv.2024.116336. Epub 2024 Apr 30.
Aflatoxin B1 (AFB1), a common mycotoxin, can occur in agricultural products. As a metabolite of AFB1, aflatoxin M1 (AFM1) mainly exist in dairy products. These two mycotoxins threaten human health, although it is unclear how they affect the function of the intestinal barrier. In this study, mice were exposed to AFB1 (0.3 mg/kg body b.w.) and AFM1(3.0 mg/kg b.w.) either individually or in combination for 28 days to explore the main differentially expressed proteins (DEPs) and the associated enriched pathways. These findings were preliminarily verified by the transcriptomic and proteomic analyses in differentiated Caco-2 cells. The results revealed that AFB1 and AFM1 exposure in mice disrupted the function of the intestinal barrier, and the combined toxicity was greater than that of each toxin alone. Further proteomic analysis in mice demonstrated that the mechanisms underlying these differences could be explained as follows: (i) lipid metabolism was enriched by AFB1-induced DEPs. (ii) protein export pathway was stimulated by AFM1-induced DEPs. (iii) cell metabolic ability was inhibited (as evidenced by changes in UDP-GT1, UDP-GT2, and Gatm6), apoptosis was induced (MAP4K3), and epithelial cell integrity was disrupted (Claudin7 and IQGAP2), resulting in more extensive intestinal damage after combined treatment. In conclusion, the hazardous impact of co-exposure to AFB1 and AFM1 from proteomic perspectives was demonstrated in the present study.
黄曲霉毒素 B1（AFB1）是一种常见的霉菌毒素，存在于农产品中。黄曲霉毒素 M1（AFM1）是 AFB1 的代谢产物，主要存在于乳制品中。这两种霉菌毒素威胁着人类的健康，尽管它们如何影响肠道屏障功能尚不清楚。在这项研究中，将小鼠暴露于 AFB1（0.3mg/kg 体重）和 AFM1（3.0mg/kg 体重）单独或联合 28 天，以探索主要差异表达蛋白（DEPs）和相关富集途径。这些发现通过分化的 Caco-2 细胞中的转录组学和蛋白质组学分析进行了初步验证。结果表明，AFB1 和 AFM1 暴露会破坏小鼠肠道屏障的功能，且联合毒性大于单独每种毒素的毒性。进一步在小鼠中的蛋白质组学分析表明，这些差异的机制可以解释如下：（i）AFB1 诱导的 DEPs 使脂质代谢富集。（ii）AFM1 诱导的 DEPs 刺激了蛋白质输出途径。（iii）细胞代谢能力受到抑制（如 UDP-GT1、UDP-GT2 和 Gatm6 的变化所表明的），诱导了细胞凋亡（MAP4K3），破坏了上皮细胞的完整性（Claudin7 和 IQGAP2），导致联合处理后更广泛的肠道损伤。总之，本研究从蛋白质组学的角度证明了 AFB1 和 AFM1 共同暴露的危害性影响。
