There is a growing body of evidence linking maternal exposure of environmental pollutants to intestinal and metabolic diseases that can be conserved across multiple generations. Here, female C57BL/6 mice were treated imazalil (IMZ) at dietary levels of 0, 0.025‰ and 0.25‰ during the gestation and lactation periods. The results demonstrated that IMZ treatment not only induced significant changes in the mucus secretion and ionic transport, but also disrupted the expression of antimicrobial peptides in the intestine of F₀, F₁ and F₂ generations. In addition, IMZ exposure altered BAs metabolism and the affected the expression levels of critical genes involved in BAs synthesis, signaling, transportation and apical uptake. The immune cell-produced cytokines were displaying extraordinary changes after IMZ exposure. In particular, whether it was in F0, F1-20d, F1-7 w or F2-20d, the expression of IL-22 had the trend of markedly increasing upon IMZ exposure. Correlation analyses revealed that the expression of IL-22 was positively correlated with the change of BAs metabolites. Together, all these results indicated that IMZ exposure was perceived as a major stress by the intestinal epithelium that strongly affected the intestinal barrier function (including mucus, CFTR, AMPs, inflammation), largely in response to an alteration of BAs metabolism.

越来越多的证据表明，母亲接触环境污染物与肠道和代谢疾病有关，这些疾病可以在多代人中保留。在此，雌性 C57BL/6 小鼠在妊娠期和哺乳期以 0、0.025‰ 和 0.25‰ 的饮食水平接受抑霉唑 (IMZ) 治疗。结果表明，IMZ处理不仅引起粘液分泌和离子转运的显着变化，而且扰乱了F ₀ 、F ₁和F ₂代肠道中抗菌肽的表达。此外，IMZ 暴露改变了 BA 的代谢，并影响了参与 BA 合成、信号传导、运输和顶端摄取的关键基因的表达水平。暴露于 IMZ 后，免疫细胞产生的细胞因子表现出非凡的变化。尤其是，无论是F0、F1-20d、F1-7w还是F2-20d，IMZ暴露后IL-22的表达均具有显着增加的趋势。相关分析显示IL-22的表达与BAs代谢物的变化呈正相关。总之，所有这些结果表明，IMZ 暴露被肠上皮视为主要压力，强烈影响肠屏障功能（包括粘液、CFTR、AMP、炎症），很大程度上是对 BA 代谢变化的反应。