Insights Into a Possible Influence on Gut Microbiota and Intestinal Barrier Function During Chronic Exposure of Mice to Imazalil

Abstract The fungicide imazalil (IMZ) is widely used to prevent and treat fungal diseases in plants and animals. Here, male adult C57BL/6 mice were exposed to 0.1, 0.5, and 2.5 mg/kg body weight IMZ for 2, 5, or 15 weeks. The microbiota in cecal contents and feces changed during chronic IMZ exposure at phylum and genus levels. Sequencing of the V3-V4 region of the bacterial 16S rRNA gene revealed a significant change in the richness of microbiota in cecal contents and feces after exposure to 2.5 mg/kg IMZ for 15 weeks. Operational taxonomic unit (OTU) analysis indicated that 31.1% of cecal OTUs and 14.0% of fecal OTUs changed after IMZ exposure. In addition, chronic IMZ exposure also disturbed the intestinal barrier function of the mice, reducing mucus secretion, decreasing the expression of cystic fibrosis transmembrane conductance regulator (CFTR)-related genes in both the ileum and colon. Molecular docking analysis revealed that key hydrogen bonds were formed by nitrogen atoms of the imidazole bond with Val440 of CFTR and Ala697 of the SLC26 family. Our data suggested that gut microbiota and intestinal barrier were potential toxicological targets of IMZ.