Integrated gut microbiota and serum metabolomics reveal glyphosate-induced hepatic injury in mice.

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-03-11 DOI:10.1177/09603271251326877
Gang Li, Yu Cheng, Xiaolei Yang, Zijun Chai, Zhihui Mu, Hong Chao, Hongjie Li, Yanbo Qi, Lei Qi, Jicheng Liu
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Abstract

IntroductionGlyphosate (GLP) is one of the most widely used herbicides in the world. However, its underlying effects on the liver remain unclear. This study aims to investigate the toxic effects and the gut microbiome- and serum metabolite-related mechanisms of GLP on the liver in mice.Methods16S rDNA sequencing and UPLC-Q-TOF-MS/MS were used to investigate the mechanisms of GLP toxicity in mice administered with 0, 50, 250 and 500 mg/kg/day GLP for 30 days.ResultsGLP induced hepatocyte edema and ballooning as well as inflammatory cell infiltration. Exposure to GLP resulted in increased levels of serum ALT, TBIL, DBIL, and GLU. Microbiota analysis at the phylum level demonstrated that the proportions of Patescibacteria decreased in the GLP-treated group. The genus-level analysis identified 11 different genera, with eight decreased and three increased in the GLP-exposed group. Metabolomics analysis of serum showed 42 differential metabolites between the GLP and control groups. The metabolic pathway enrichment analysis revealed that the pentose phosphate pathway (PPP) and pyrimidine metabolism were significantly activated. Spearman analysis showed that the changes in the differential metabolites of the PPP and pyrimidine metabolism and gut microbiota were strongly associated with the biochemical index.DiscussionIn conclusion, GLP exposure induces hepatic injury through alterations in the gut microbiome and metabolic pathways, particularly by activating the pentose phosphate pathway and pyrimidine metabolism.

综合肠道微生物群和血清代谢组学揭示草甘膦诱导的小鼠肝损伤。
草甘膦(GLP)是世界上使用最广泛的除草剂之一。然而,其对肝脏的潜在影响尚不清楚。本研究旨在探讨GLP对小鼠肝脏的毒性作用及其肠道微生物组和血清代谢物相关机制。方法采用16s rDNA测序法和UPLC-Q-TOF-MS/MS方法研究GLP对小鼠的毒性作用机制,分别给药0、50、250和500 mg/kg/d。结果glp可诱导大鼠肝细胞水肿、水肿及炎症细胞浸润。暴露于GLP导致血清ALT、TBIL、DBIL和GLU水平升高。门水平的微生物群分析表明,glp处理组的Patescibacteria比例下降。属水平分析鉴定了11个不同的属,在glp暴露组中有8个减少,3个增加。血清代谢组学分析显示,GLP组与对照组之间存在42种差异代谢物。代谢途径富集分析显示戊糖磷酸途径(PPP)和嘧啶代谢被显著激活。Spearman分析显示,PPP、嘧啶代谢和肠道菌群的差异代谢物变化与生化指标密切相关。总之,GLP暴露通过改变肠道微生物组和代谢途径,特别是通过激活戊糖磷酸途径和嘧啶代谢,诱导肝损伤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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