Hepatoprotective effect of curcumin against bisphenol A-induced hepatic steatosis via modulating gut microbiota dysbiosis and related gut-liver axis activation in CD-1 mice
Hepatoprotective effect of curcumin against bisphenol A-induced hepatic steatosis via modulating gut microbiota dysbiosis and related gut-liver axis activation in CD-1 mice
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DOI：
10.1016/j.jnutbio.2022.109103
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发表时间：
2022-07-21
影响因子：
5.6
通讯作者：
Feng, Dan
中科院分区：
文献类型：
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作者：
Hong, Ting;Jiang, Xin;Feng, Dan
长期接触低剂量双酚A（BPA）已成为全球性的公共卫生问题。我们以前的工作表明，低剂量BPA暴露会导致肠道微生物生态失调和肝脏脂肪变性。姜黄素是从姜黄中提取的一种多酚类物质，具有抑制肝脏脂质蓄积的作用，姜黄素是否能通过改善肠道植物群和调节肠-肝轴来减轻BPA诱导的肝脏脂肪变性尚有待进一步研究。雄性CD-1小鼠用补充或不补充姜黄素的BPA污染的饮食喂养24周。补充姜黄素可显著改善BPA诱导的肝脏脂肪堆积和肝脂肪变性。通过16 S rRNA测序进行的肠道微生物群分析显示，在BPA喂养的小鼠中，变形菌门和厚壁菌门/拟杆菌门的相对丰度增加，并且这种改变被姜黄素治疗逆转。Akkermansia被认为是一种潜在的益生菌，在BPA暴露后显着减少，并在添加姜黄素后恢复到对照水平。此外，姜黄素还能逆转BPA诱导的小肠紧密连接蛋白表达下调，改善肠道通透性，降低血清脂多糖水平，并抑制BPA诱导的肝脏Toll样受体4 /核因子-KB（TLR 4/NF-KB）通路的激活。提示姜黄素对BPA诱导的肝脂肪变性具有保护作用，其机制可能是通过其益生元作用维持肠道植物群平衡，改善肠道屏障功能，从而减轻血清脂多糖引发的肝脏炎症反应。我们的工作为姜黄素作为BPA介导的肝脂肪变性的潜在营养疗法提供了证据。(C)2022爱思唯尔公司All rights reserved.
Chronic exposure to low-dose bisphenol A (BPA) has become a global problem of public health. Our previous work showed that low-dose BPA exposure caused gut microbial dysbiosis and hepatic steatosis. Curcumin, a polyphenol extracted from turmeric, has an inhibitory effect on liver lipid accumulation, whether curcumin can alleviate BPA-induced hepatic steatosis through improving intestinal flora and modulating gut-liver axis remains to be elucidated. Male CD-1 mice were fed with BPA-contaminated diet supplemented with or not with curcumin for 24 weeks. Curcumin supplementation markedly ame-liorated liver fat accumulation and hepatic steatosis induced by BPA. Gut microbiota analysis via 16S rRNA sequencing revealed that the relative abundance of Proteobacteria and Firmicutes/Bacteroidetes ratio were increased in BPA-fed mice, and this alteration was reversed by curcumin treatment. Akkermansia, which was recognized as a potential probiotic, was significantly reduced after BPA exposure and was restored to the control level with curcumin addition. Furthermore, curcumin supplementation reversed the down-regulation of intestinal tight junction protein expressions (zona occludens-1 and occludin), im-proved increased gut permeability, reduced serum lipopolysaccharide level and suppressed the activation of hepatic toll-like receptor 4 / nuclear factor -KB (TLR4/NF-KB) pathway induced by BPA. These results indicated that the protective effect of curcumin against hepatic steatosis induced by BPA and further revealed that its mechanism might be its prebiotic effect on maintaining intestinal flora homeostasis and improving intestinal barrier function, consequently reducing serum lipopolysaccharide-triggered inflammatory response in the liver. Our work provides evidence for curcumin as a potential nutritional therapy for BPA-mediated hepatic steatosis. (C) 2022 Elsevier Inc. All rights reserved.