Abstract

Dibutyl phthalate (DBP), a kind of typical environmental pollutant, is widely used as plasticizers, and its neurotoxicity and developmental toxicity have been found in recent years. However, whether oral DBP exposure will affect the homeostasis of gut microbiota and its adverse response in liver of mammalians remain unclear. In the present study, 10-week experimental cycles of vehicle or DBP (0.1 and 1 mg/kg) were given to 6-week-old C57BL/6J mice by oral gavage. Our results revealed that the body weight of mice was increased after exposure to both low and high doses of DBP. The serum levels of hepatic triglyceride and total cholesterol were significantly increased in response to both doses of DBP. In addition, some pivotal genes related to lipogenesis were also increased in liver at the mRNA level. Evaluation of gut microbiota by 16S rRNA sequencing technology showed that 0.1 mg/kg DBP exposure significantly affected gut microbiota at the phylum and genus levels. Moreover, DBP exposure decreased mucus secretion and caused inflammation in the gut, leading to the impairment of intestinal barrier function. Exposure to DBP inhibited the expression of peroxisome proliferator-activated receptor-γ and activated the expression of nuclear factor kappa B. In addition, DBP exposure increased the level of lipopolysaccharide in serum, and increased the expression of toll-like receptor 4 and the levels of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha, in the liver. These results indicated that exposure to DBP disturbed the homeostasis of gut microbiota, induced hepatic lipid metabolism disorder, and caused liver inflammation in mice via the related gut–liver axis signaling pathways.

中文翻译：

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邻苯二甲酸二丁酯的暴露会损害脂质代谢，并通过干扰与微生物群有关的肠-肝轴而引起炎症

摘要

邻苯二甲酸二丁酯（DBP）是一种典型的环境污染物，被广泛用作增塑剂，近年来已发现其神经毒性和发育毒性。但是，口服DBP暴露是否会影响肠道菌群的体内平衡及其在哺乳动物肝脏中的不良反应尚不清楚。在本研究中，通过强饲法对6周龄的C57BL / 6J小鼠进行了10周的媒介物或DBP实验周期（0.1和1 mg / kg）。我们的结果表明，暴露于低剂量和高剂量的DBP后，小鼠的体重都会增加。两种剂量的DBP均使肝甘油三酯和总胆固醇的血清水平显着升高。此外，肝脏中与脂肪生成有关的一些关键基因在mRNA水平也有所增加。通过16S rRNA测序技术评估肠道菌群，发现0.1 mg / kg DBP暴露显着影响门和属水平的肠道菌群。此外，DBP暴露会减少粘液分泌并导致肠道发炎，从而导致肠屏障功能受损。暴露于DBP会抑制过氧化物酶体增殖物激活的受体γ的表达，并激活核因子κB的表达。此外，DBP暴露会增加血清中的脂多糖水平，并增加toll样受体4的表达及其水平。肝中炎性细胞因子（例如白介素（IL）-1β，IL-6和肿瘤坏死因子α）的表达。这些结果表明，暴露于DBP会扰乱肠道菌群的体内平衡，诱发肝脂质代谢紊乱，