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肠道环境紊乱与全氟辛烷磺酸暴露引起的组织损伤有关。

Intestinal environmental disorders associate with the tissue damages induced by perfluorooctane sulfonate exposure.

机构信息

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, PR China; School of Food Science and Technology, Jiangnan University, Wuxi, 214122, PR China.

Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, 214122, PR China.

出版信息

Ecotoxicol Environ Saf. 2020 Jul 1;197:110590. doi: 10.1016/j.ecoenv.2020.110590. Epub 2020 Apr 10.

Abstract

Perfluorooctane sulfonate (PFOS) is a recently identified and persistent organic pollutant that becomes enriched in living organisms via bioaccumulation and the food chain. PFOS can induce various disorders, including liver toxicity, neurotoxicity and metabolic dysregulation. Most recent studies have shown a close association of the gut microbiota with the occurrence of diseases. However, few studies have explored the effects of PFOS on the gut environment, including the intestinal flora and barrier. In this study, we evaluated the effects of PFOS in C57BL/6J male mice and explored the relationship between tissue damage and the gut environment. Mice were orally exposed to PFOS for 16 days. Liver damage was assessed by examining the inflammatory reaction in the liver and serum liver enzyme concentrations. Metabolic function was assessed by the hepatic cholesterol level and the serum concentrations of glucose, high-density lipoprotein cholesterol, total cholesterol and triglycerides. Intestinal environmental disorders were assessed by evaluating the gut microbiota, SCFAs production, inflammatory reactions and intestinal tight junction protein expression. Our results indicated that PFOS affected inflammatory reactions in the liver and colon and promoted the development of metabolic disorders (especially of cholesterol and glucose metabolism). Moreover, PFOS dysregulated various populations in the gut microbiota (e.g., Firmicutes, Bacteroides, Proteobacteria, Gammaproteobacteria, Clostridiales, Enterobacteriales, Lactobacillales, Erysipelotrichaceae, Rikenellaceae, Ruminococcaceae and Blautia) and induced a loss of gut barrier integrity by reducing short-chain fatty acids (SCFAs) production and intestinal tight junction protein expression. A Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis mainly identified metabolic pathways (e.g., the adipocytokine signalling pathway), endocrine system pathways (e.g., steroid hormone biosynthesis, flavonoid biosynthesis), the latter of which is widely considered to be associated with metabolism. Overall, our results suggest that PFOS damages various aspects of the gut environment, including the microbiota, SCFAs and barrier function, and thereby exacerbates the toxicity associated with liver, gut and metabolic disorders.

摘要

全氟辛烷磺酸(PFOS)是一种新发现的持久性有机污染物,它通过生物积累和食物链在生物体中富集。PFOS 可引起多种疾病,包括肝毒性、神经毒性和代谢紊乱。最近的研究表明,肠道微生物群与疾病的发生密切相关。然而,很少有研究探讨 PFOS 对肠道环境的影响,包括肠道菌群和肠道屏障。在本研究中,我们评估了 PFOS 对 C57BL/6J 雄性小鼠的影响,并探讨了组织损伤与肠道环境之间的关系。小鼠经口暴露于 PFOS 16 天。通过检测肝脏的炎症反应和血清肝酶浓度来评估肝损伤。通过肝胆固醇水平和血清葡萄糖、高密度脂蛋白胆固醇、总胆固醇和甘油三酯浓度来评估代谢功能。通过评估肠道微生物群、短链脂肪酸(SCFA)产生、炎症反应和肠道紧密连接蛋白表达来评估肠道环境紊乱。我们的结果表明,PFOS 影响肝脏和结肠的炎症反应,并促进代谢紊乱(特别是胆固醇和葡萄糖代谢)的发展。此外,PFOS 扰乱了肠道微生物群中的各种种群(例如厚壁菌门、拟杆菌门、变形菌门、γ-变形菌门、梭菌目、肠杆菌目、乳杆菌目、毛螺菌科、理研菌科、瘤胃球菌科和布劳特氏菌属),并通过减少短链脂肪酸(SCFA)产生和肠道紧密连接蛋白表达导致肠道屏障完整性丧失。未观察到状态重建的群落系统发育分析(PICRUSt)分析主要鉴定了代谢途径(例如,脂肪细胞因子信号通路)和内分泌系统途径(例如,甾体激素生物合成、类黄酮生物合成),后者被广泛认为与代谢有关。总体而言,我们的研究结果表明,PFOS 损害了肠道环境的多个方面,包括微生物群、SCFAs 和屏障功能,从而加剧了与肝脏、肠道和代谢紊乱相关的毒性。

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