College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, China; Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Interdisciplinary Research Academy, Zhejiang Shuren University, Hangzhou, 310015, China.
College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, China.
Chemosphere. 2022 Nov;307(Pt 4):136141. doi: 10.1016/j.chemosphere.2022.136141. Epub 2022 Aug 23.
The triazole fungicide prothioconazole (PTC) can cause adverse effects in animals, and its main metabolite prothioconazole-desthio (PTC-d) is even much more harmful. However, the toxic effects of PTC and PTC-d on the liver-gut axis of mice are still unknown. In the present experiment, we found that oral exposure to PTC and PTC-d increased total bile acids (TBAs) levels in the serum, liver, and feces. Correspondingly, the transcription of genes involved in bile acids (BAs) disposition was significantly influenced by PTC or PTC-d exposure. Furthermore, the BAs composition of serum BAs was analyzed by LC-MS, and the results indicated that PTC and PTC-d exposure changed the BAs composition, lowered the ratio of conjugated/unconjugated BAs, elevated the ratio of CA/b-MCA, and enhanced the hydrophobicity of BAs pool. 16s RNA gene sequencing of the DNA from colonic contents uncovered that PTC and PTC-d exposure altered the relative abundance and constitution of intestinal microbiota, increasing the relative level of Lactobacillus with bile salt hydrolase (BSH) activity. Furthermore, PTC and PTC-d exposure impaired the gut barrier function, causing an increase in mucus secretion. In particular, the effects of PTC-d on some endpoints in the BAs metabolism and gut barrier function had been proven to be more significant than the parent compound PTC. All these findings draw attention to the health risk of PTC and PTC-d exposure in regulating BAs metabolism, which might lead to some metabolic disorders and occur of related diseases in animals.
三唑类杀菌剂丙硫菌唑（PTC）可对动物产生不良影响，其主要代谢物丙硫菌唑脱巯基（PTC-d）的危害性甚至更大。然而，PTC 和 PTC-d 对小鼠肝肠轴的毒性作用尚不清楚。在本实验中，我们发现口服暴露于 PTC 和 PTC-d 会增加血清、肝脏和粪便中的总胆汁酸（TBAs）水平。相应地，PTC 或 PTC-d 暴露显著影响参与胆汁酸（BAs）处置的基因的转录。此外，通过 LC-MS 分析血清 BAs 的 BAs 组成，结果表明 PTC 和 PTC-d 暴露改变了 BAs 组成，降低了结合/未结合 BAs 的比例，增加了 CA/b-MCA 的比例，并增强了 BAs 池的疏水性。结肠内容物的 DNA 16s RNA 基因测序揭示，PTC 和 PTC-d 暴露改变了肠道微生物群的相对丰度和组成，增加了具有胆盐水解酶（BSH）活性的乳杆菌的相对水平。此外，PTC 和 PTC-d 暴露损害了肠道屏障功能，导致粘液分泌增加。特别是，PTC-d 在 BAs 代谢和肠道屏障功能的某些终点上的作用被证明比母体化合物 PTC 更为显著。所有这些发现都引起了人们对 PTC 和 PTC-d 暴露在调节 BAs 代谢方面的健康风险的关注，这可能导致动物发生一些代谢紊乱和相关疾病。
