College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.
Guangdong Provincial Key Laboratory of Food Quality and Safety, South China Agricultural University, Guangzhou 510642, China.
Acta Biochim Biophys Sin (Shanghai). 2020 Dec 29;52(12):1382-1393. doi: 10.1093/abbs/gmaa128.
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.
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，近年来发现其具有神经毒性和发育毒性。然而，口服 DBP 暴露是否会影响哺乳动物肠道微生物群的内稳态及其在肝脏中的不良反应尚不清楚。在本研究中，通过口服灌胃给予 6 周龄 C57BL/6J 小鼠 10 周的实验周期的载体或 DBP（0.1 和 1mg/kg）。我们的结果表明，暴露于低剂量和高剂量 DBP 后，小鼠的体重增加。血清肝甘油三酯和总胆固醇水平均显著升高。此外，肝脏中一些与脂肪生成相关的关键基因在 mRNA 水平上也增加。通过 16S rRNA 测序技术评估肠道微生物群，发现 0.1mg/kgDBP 暴露在门和属水平上显著影响肠道微生物群。此外，DBP 暴露减少了粘液分泌并引起肠道炎症，导致肠道屏障功能受损。DBP 暴露抑制过氧化物酶体增殖物激活受体-γ 的表达并激活核因子 kappa B 的表达。此外，DBP 暴露增加了血清中脂多糖的水平，并增加了肝脏中 toll 样受体 4 的表达和炎症细胞因子（如白细胞介素（IL）-1β、IL-6 和肿瘤坏死因子 alpha）的水平。这些结果表明，DBP 暴露通过相关的肠道-肝脏轴信号通路扰乱了肠道微生物群的内稳态，诱导了肝脏脂质代谢紊乱，并导致了小鼠肝脏炎症。
