连续皮肤暴露于三氯卡班会扰乱小鼠肝肠轴的体内稳态：从代谢相互作用和微生物组变化中获得的见解,Environmental Science & Technology

当前位置： X-MOL 学术 › Environ. Sci. Technol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

连续皮肤暴露于三氯卡班会扰乱小鼠肝肠轴的体内稳态：从代谢相互作用和微生物组变化中获得的见解
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2021-03-10 , DOI: 10.1021/acs.est.0c08273
Hongna Zhang ₁ , Yanshan Liang ₁ , Pengfei Wu ₁ , Xianru Shi ₁ , Guodong Zhang ₂ , Zongwei Cai ₁

Affiliation

人们通过与个人护理品和消费品直接皮肤接触而不断暴露于抗菌三氯卡班（TCC），但长期皮肤暴露于TCC的安全性仍然未知。在本文中，我们使用小鼠模型评估了在与人有关的浓度下连续皮下施用TCC的潜在健康风险。经皮吸收后，TCC在血液中循环并大量进入肝肠轴进行代谢处置。非靶向代谢组学方法表明，TCC暴露扰动了小鼠肝脏的体内稳态，氧化应激的增加和甲基化能力的降低证明了这一点，从而导致氧化损伤，上游糖酵解和叶酸依赖性一碳代谢的增强。同时，TCC通过羟基化，脱氯，甲基化，葡萄糖醛酸化，硫酸化和谷胱甘肽结合。TCC衍生的异种生物随后被排泄到肠道中，葡萄糖醛酸和硫酸盐代谢物可以被肠道菌群进一步解结合成活性的游离形式。另外，微生物群落分析表明肠道微生物组的组成响应于TCC暴露而改变，表明肠道稳态的扰动。一起，通过追踪异种-生物相互作用微生物群落分析表明，肠道微生物组的组成响应于TCC暴露而改变，表明肠道稳态的扰动。一起，通过追踪异种-生物相互作用微生物群落分析表明，肠道微生物组的组成响应于TCC暴露而改变，表明肠道稳态的扰动。一起，通过追踪异种-生物相互作用在体内，这项研究为皮肤吸收的TCC对肝脏和肠道微环境的潜在影响提供了新颖的见解。

"点击查看英文标题和摘要"

Continuous Dermal Exposure to Triclocarban Perturbs the Homeostasis of Liver–Gut Axis in Mice: Insights from Metabolic Interactions and Microbiome Shifts

Humans are constantly exposed to antimicrobial triclocarban (TCC) via direct skin contact with personal care and consumer products, but the safety of long-term dermal exposure to TCC remains largely unknown. Herein, we used a mouse model to evaluate the potential health risks from the continuous dermal application of TCC at human-relevant concentrations. After percutaneous absorption, TCC circulated in the bloodstream and largely entered the liver–gut axis for metabolic disposition. Nontargeted metabolomics approach revealed that TCC exposure perturbed mouse liver homeostasis, as evidenced by the increased oxidative stress and impaired methylation capacity, leading to oxidative damage and enhancement of upstream glycolysis and folate-dependent one-carbon metabolism. Meanwhile, TCC was transformed in the liver through hydroxylation, dechlorination, methylation, glucuronidation, sulfation, and glutathione conjugation. TCC-derived xenobiotics were subsequently excreted into the gut, and glucuronide and sulfate metabolites could be further deconjugated by the gut microbiota into their active free forms. In addition, microbial community analysis showed that the composition of gut microbiome was altered in response to TCC exposure, indicating the perturbation of gut homeostasis. Together, through tracking the xenobiotic–biological interactions in vivo, this study provides novel insights into the underlying impacts of dermally absorbed TCC on the liver and gut microenvironments.

更新日期：2021-04-20

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南