School of Horticulture and Plant Protection, Yangzhou University/Joint International Research Laboratory of Agriculture & Agri-Product Safety, Yangzhou, Jiangsu 225009, China.
Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China.
J Agric Food Chem. 2021 Nov 17;69(45):13436-13447. doi: 10.1021/acs.jafc.1c05508. Epub 2021 Nov 4.
The environmental risks of prothioconazole (PTC), a popular agricultural fungicide, and its main metabolite, prothioconazole-desthio (PTCd), have attracted more and more attention recently. In this study, the adverse effects of PTC and PTCd on liver function in mice and their underlying mechanisms have been systematically studied from the perspective of gut microbiota. Combining the results of physiological, biochemical, and histopathological analysis showed that PTC and PTCd exposure could cause lipid accumulation and inflammation in the liver of mice. In addition, exposure to PTC and PTCd could also significantly affect the transcriptome of liver tissue, leading to disorders of lipid metabolism of the liver. Particularly, the abundances of bacteria in liver tissues were significantly increased with PTC and PTCd exposure. Further results show that PTC and PTCd could affect the expression of genes related to inflammation and the barrier function in colon tissue, leading to intestinal dysfunction in mice. Last but not least, the results based on 16S rRNA gene sequencing and H NMR metabolomics analysis showed that exposure to PTC and PTCd could cause gut microbiota imbalances and cecal content metabolic profile disorders. In short, this study found that PTC and PTCd exposure could cause liver damage in mice by changing the gut microbiota, disrupting the intestinal barrier function and promoting bacterial translocation. These results clarified the key role of gut microbiota in liver damage induced by PTC and PTCd in mice and proposed a new insight into the mechanisms of liver toxicity induced by pesticides through the dialogue of the gut-liver axis.
丙硫菌唑（PTC）是一种常用的农业杀菌剂，其主要代谢物丙硫菌唑脱巯基（PTCd）的环境风险近来受到越来越多的关注。本研究从肠道微生物群的角度系统研究了 PTC 和 PTCd 对小鼠肝功能的不良影响及其潜在机制。生理、生化和组织病理学分析结果表明，PTC 和 PTCd 暴露可导致小鼠肝脏脂质蓄积和炎症。此外，PTC 和 PTCd 暴露还可显著影响肝脏组织的转录组，导致肝脏脂质代谢紊乱。特别是，暴露于 PTC 和 PTCd 可使肝脏组织中细菌的丰度显著增加。进一步的结果表明，PTC 和 PTCd 可影响结肠组织中与炎症和屏障功能相关基因的表达，导致小鼠肠道功能障碍。最后但并非最不重要的是，基于 16S rRNA 基因测序和 H NMR 代谢组学分析的结果表明，PTC 和 PTCd 的暴露可导致肠道微生物群失衡和盲肠内容物代谢谱紊乱。总之，本研究发现，PTC 和 PTCd 暴露可通过改变肠道微生物群、破坏肠道屏障功能和促进细菌易位导致小鼠肝脏损伤。这些结果阐明了肠道微生物群在 PTC 和 PTCd 诱导小鼠肝脏损伤中的关键作用，并通过肠-肝轴的对话提出了农药诱导肝脏毒性的新机制。
