黄曲霉毒素M1（AFM1）是牛奶中主要的霉菌毒素，赭曲霉毒素A（OTA）是谷物等食品中主要的霉菌毒素。“牛奶+谷物”已逐步成为常见的家庭膳食模式。在这种模式下，两种霉菌毒素在人体内共存的交互作用及其潜在危害的机制值得深入研究。本团队前期的细胞试验发现，AFM1和OTA共存时对肠分化Caco-2细胞有协同毒性作用，运用联合组学分析发现，转录后调控在霉菌毒素损伤肠道屏障中发挥了重要作用，但具体机制不明。在此基础上，本项目拟采用活体小鼠模型，以肠道屏障中紧密连接蛋白（TJ蛋白）为切入点，采用全转录组学进一步解析多种RNA信息，进行鉴定和关联分析，得到竞争内源性RNA（ceRNA）调控网络，结合小鼠原代小肠上皮细胞模型验证其中核心基因的关联性及功能，尝试筛选霉菌毒素介导引发肠道屏障损伤的分子标志物。研究结果将为解析和评估霉菌毒素交互作用这一新的食品安全隐患提供重要科学依据。

Aflatoxin M1 (AFM1) is the main mycotoxin in milk, and ochratoxin A (OTA) is the main mycotoxin in foods such as cereals. “Milk+Cereal” has gradually become a common family dietary pattern. Under this model, the content of AFM1 or OTA alone may not exceed the standard, but the potential harm of coexistence in the human body and the mechanism of its interaction are worthy of further study. Preceding researches of our team demonstrated a synergic action of AFM1 and OTA to human intestinal Caco-2 cell line, with an obviously enhanced virulence compared to individual toxin alone. In addition, previous studies also reported that the translational process played a vital role in the regulation of mycotoxin-induced compromised intestinal barrier, which summarized from the integrative analysis of transcriptome and proteome. However, further in vivo trials are needed to profoundly understand its underlying mechanism. ICR mice model is selected for determination of a series of intestinal phenotypes induced by toxins, especially for the tight junction proteins (TJ proteins). The whole transcriptome analysis is used to analyze a cross-talk within several kinds of RNA (mRNA, lncRNA, circRNA, miRNA), in which a global competing endogenous RNA (ceRNA) regulatory network responding to interaction of both toxins is set up, and non-coding RNA-regulated mRNAs will be paid more attention. What’s more, significant node genes in the net can also be hunted and confirmed by relevant mouse primary cell model validation. Based on this, potential clinical diagnostic biomarkers that specifically reflect the intestinal barrier injury are screened. This project can provide an important scientific basis for the analysis and evaluation of multi-mycotoxins, the new food safety hazards.