肠道菌群
胆汁酸
法尼甾体X受体
脂质代谢
失调
鹅去氧胆酸
胆固醇
内科学
内分泌学
邻苯二甲酸盐
FGF19型
新陈代谢
生物化学
胆酸
化学
粪便
生物
甾醇
胆固醇7α羟化酶
CYP8B1
排泄
胆酸
核受体
受体
医学
转录因子
成纤维细胞生长因子
有机化学
基因
作者
Zhen Yu,Zhenhua Shi,Zhihua Zheng,Junyong Han,Wencong Yang,Rongmei Lu,Wei Lin,Yuanyuan Zheng,Daoshun Nie,Gang Chen
出处
期刊:Chemosphere
[Elsevier]
日期:2021-01-01
卷期号:263: 127959-127959
被引量:20
标识
DOI:10.1016/j.chemosphere.2020.127959
摘要
Di(2-ethylhexyl) phthalate (DEHP) is one of the most widespread environmental contaminants worldwide because of its massive production, extensive use in common products, and liability to leach from products. This study investigated the mechanisms of DEHP mediated alteration of lipid metabolism. Rats were treated with 0.5 mg kg −1 d −1 of DEHP for 23 weeks. Results showed that the treatment induced cholesterol imbalance. Further fecal transplantation experiments corroborated the involvement of gut microbiota in DEHP-induced cholesterol imbalance. In addition, 16S rRNA gene sequencing analysis of cecal contents showed that DEHP disrupted the gut microbiota diversity in rats and increased the ratio of Firmicutes to Bacteroidetes . Further cecal metabolomic analyses, bile salt hydrolase enzyme activity, and gene expression examination revealed that chronic DEHP exposure generated a bile acid profile in the gut that is a more potent activator of farnesoid X receptor (FXR). The activation of FXR in the gut induced the expression of fibroblast growth factor 15, which subsequently suppressed cytochrome P450 family 7 subfamily A member 1 in the liver and bile acid synthesis. These results suggest that DEHP might induce cholesterol imbalance by regulating bile acid metabolism via the remodeling of the gut microbiota. • We studied the effect of chronic low-dose DEHP exposure on lipid metabolism in rats. • Chronic low-dose DEHP exposure resulted in cholesterol imbalance and gut microbiome dysbiosis. • Chronic low-dose DEHP suppressed bile acid synthesis via upregulating the ileal FXR–FGF15 axis.
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