<br>草甘膦暴露对肠道-肝脏轴的影响：草鱼（Ctenopharyngodon idellus）的代谢组学和机制分析,Science of the Total Environment

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草甘膦暴露对肠道-肝脏轴的影响：草鱼（Ctenopharyngodon idellus）的代谢组学和机制分析
Science of the Total Environment ( IF 8.2 ) Pub Date : 2023-08-04 , DOI: 10.1016/j.scitotenv.2023.166062
Biao Yan ₁ , Yumiao Sun ₂ , Kaiyu Fu ₂ , Yindan Zhang ₂ , Lei Lei ₂ , Jun Men ₃ , Yongyong Guo ₄ , Shengmin Wu ₅ , Jian Han ₄ , Bingsheng Zhou ₄

Affiliation

草甘膦是全球使用最广泛的除草剂之一，对非目标水生生物具有潜在危害。然而，关于对代谢稳态影响的环境健康风险和潜在机制仍不清楚。在这里，我们研究了草鱼暴露于草甘膦后的生物积累、代谢紊乱和机制。检测到草甘膦及其主要代谢物氨基甲基膦酸在肠道中的积累较高。肠道炎症、屏障损伤和肝脏脂肪变性是由草甘膦暴露引起的。甘油三酯降低、血清中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，肠道菌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在肠道中产生更高的生物蓄积，从而诱发肠肝损伤、肠道菌群失调和胆汁酸代谢稳态紊乱;那么肠-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于水生环境中鱼类的代谢健康风险。

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Effects of glyphosate exposure on gut–liver axis: Metabolomic and mechanistic analysis in grass carp (Ctenopharyngodon idellus)

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.

更新日期：2023-08-04

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