Maternal exposure to imazalil disrupts intestinal barrier and bile acids enterohepatic circulation tightly related IL-22 expression in F0, F1 and F2 generations of mice

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 parts per thousand and 0.25 parts per thousand 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 F-0, F-1 and F-2 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.