Co-exposure ochratoxin A and triadimefon influenced the hepatic glucolipid metabolism and intestinal micro-environment in mice

Ochratoxin A (OTA) is a mycotoxin, and triadimefon (TDF) is a triazole fungicide. These compounds are prevalent in the environment, and their residues have been detected in crops. However, the precise health risks associated with mycotoxins and fungicides are not fully elucidated. In this work, five-week-old mice were gavage with OTA (0.3 and 1.5 mg/kg/day), TDF (10 and 50 mg/kg/day), and OTA + TDF (0.3 + 10 and 1.5 + 50 mg/kg/day) for 28 days. Exposure to OTA, TDF, and OTA + TDF led to significant alterations in liver total cholesterol (TC), triglyceride (TG), and glucose (GLU) levels, as well as in genes associated with glycolipid metabolism in mice. Reduced acylcarnitine levels in serum indicated that OTA, TDF, and co-exposure inhibited fatty acid (FA) β-oxidation. Furthermore, OTA and TDF disrupted the integrality of the gut barrier function and altered the structure of the intestinal microbiota. These findings suggested that OTA, TDF, and their co-exposure might disrupt the intestinal barrier, alter the structure of the microbiota, and subsequently inhibit FA β-oxidation, indicating the interference of OTA and TDF with glycolipid-related intestinal barrier dysfunction. Moreover, our data revealed a toxic additive effect between OTA and TDF, providing a foundation for assessing the combined toxicity risk of mycotoxins and fungicides.