Oral Exposure to Epoxiconazole Disturbed the Gut Micro-Environment and Metabolic Profiling in Male Mice

Epoxiconazole (EPX), a triazole fungicide, is widely used in agriculture to control pests and diseases. High residual and occupational exposure to EPX increases health risks, and evidence of potential harm to mammals remains to be added. In the present study, 6-week-old male mice were exposed to 10 and 50 mg/kg bw EPX for 28 days. The results showed that EPX significantly increased the liver weights. EPX also decreased the mucus secretion of the colon and altered intestinal barrier function in mice including a reduced expression of some genes (<i>Muc2</i>, <i>meprinβ</i>, <i>tjp1</i>). Moreover, EPX altered the composition and abundance of gut microbiota in the colon of mice. The alpha diversity indices (Shannon, Simpson) in the gut microbiota increased after exposure to EPX for 28 days. Interestingly, EPX increased the ratio of <i>Firmicutes</i> to <i>Bacteroides</i> and the abundance of other harmful bacteria including <i>Helicobacter</i> and <i>Alistipes</i>. Based on the untargeted metabolomic analysis, it was found that EPX altered the metabolic profiles of the liver in mice. KEGG analysis of differential metabolites revealed that EPX disrupted the pathway related to glycolipid metabolism, and the mRNA levels of related genes were also confirmed. In addition, the correlation analysis showed that the most altered harmful bacteria were associated with some significantly altered metabolites. The findings highlight that EPX exposure changed the micro-environment and lipid metabolism disturbance. These results also suggest that the potential toxicity of triazole fungicides to mammals cannot be ignored.