Yan Biao, Sun Yumiao, Fu Kaiyu, Zhang Yindan, Lei Lei, Men Jun, Guo Yongyong, Wu Shengmin, Han Jian, Zhou Bingsheng
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academic of Sciences, Wuhan 430072, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China; Xianning Engineering Research Center for Healthy Environment, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, PR China.
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academic of Sciences, Wuhan 430072, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
Sci Total Environ. 2023 Dec 1;902:166062. doi: 10.1016/j.scitotenv.2023.166062. Epub 2023 Aug 4.
Glyphosate, one of the most widely used herbicide worldwide, is potentially harmful to non-target aquatic organisms. However, the environmental health risks regarding impacts on metabolism homeostasis and underlying mechanisms remain unclear. Here we investigated bioaccumulation, metabolism disorders and mechanisms in grass carp after exposure to glyphosate. Higher accumulation of glyphosate and its major metabolite, aminomethylphosphonic acid, in the gut was detected. Intestinal inflammation, barrier damage and hepatic steatosis were caused by glyphosate exposure. Lipid metabolism disorder was confirmed by the decreased triglyceride, increased total cholesterol and lipoproteins in serum and decreased visceral fat. Metabolomics analysis found that glyphosate exposure significantly inhibited bile acids biosynthesis in liver with decreased total bile acids content, which was further supported by significant downregulations of cyp27a1, cyp8b1 and fxr. Moreover, the dysbiosis of gut microbiota contributed to the inflammation in liver and gut by increasing lipopolysaccharide, as well as to the declined bile acids circulation by reducing secondary bile acids. These results indicated that exposure to environmental levels of glyphosate generated higher bioaccumulation in gut, where evoked enterohepatic injury, intestinal microbiota dysbiosis and disturbed homeostasis of bile acids metabolism; then the functional dysregulation of the gut-liver axis possibly resulted in ultimate lipid metabolism disorder. These findings highlight the metabolism health risks of glyphosate exposure to fish in aquatic environment.
草甘膦是全球使用最广泛的除草剂之一，可能对非靶标水生生物有害。然而，关于其对代谢稳态的影响及潜在机制的环境健康风险仍不清楚。在此，我们研究了草鱼暴露于草甘膦后的生物累积、代谢紊乱及机制。检测到草甘膦及其主要代谢产物氨基甲基膦酸在肠道中的累积量更高。草甘膦暴露导致肠道炎症、屏障损伤和肝脏脂肪变性。血清中甘油三酯降低、总胆固醇和脂蛋白增加以及内脏脂肪减少证实了脂质代谢紊乱。代谢组学分析发现，草甘膦暴露显著抑制肝脏中胆汁酸的生物合成，总胆汁酸含量降低，cyp27a1、cyp8b1和fxr的显著下调进一步支持了这一点。此外，肠道微生物群的失调通过增加脂多糖导致肝脏和肠道炎症，并通过减少次级胆汁酸导致胆汁酸循环下降。这些结果表明，暴露于环境水平的草甘膦会在肠道中产生更高的生物累积，引发肠肝损伤、肠道微生物群失调和胆汁酸代谢稳态紊乱；然后，肠-肝轴的功能失调可能导致最终的脂质代谢紊乱。这些发现突出了草甘膦暴露对水生环境中鱼类的代谢健康风险。
