| 项目编号 |
PRJCA020045 |
| 项目标题 |
Roseburia intestinalis relieves intrahepatic cholestasis of pregnancy through bile acid/FXR-FGF15 in rats |
| 涉及领域 |
metabolomics |
| 数据类型 |
metabolomics
|
| 物种名称 |
Rattus
|
| 描述信息 |
Previous research has demonstrated significant differences in intestinal flora between pregnant women with intrahepatic cholestasis of pregnancy (ICP) and healthy pregnant women. However, it remains unclear which specific intestinal microflora is associated with ICP and how changes in intestinal microflora regulate the potential mechanism of host bile acid metabolism. The objective of our study is to identify the key bacteria involved in ICP rats and explore the underlying mechanism. We established an ICP rat model using 17-α-ethinylestradiol. We collected rat feces for metagenomic sequencing and found that Roseburia intestinalis (R.I) is the key bacteria in ICP. Transplantation of R.I reduced total serum bile acid levels, reduced bile acid synthesis, increased bile acid transport, restored intestinal barrier function, alleviated liver inflammation and immune imbalance, reduced fecal chenodeoxycholic acid, and activated the intestinal farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) signaling pathway in ICP rats. We used the FXR antagonist Z-Guggulsterone (Z-Gu) to verify the key role of FXR in ICP and found that Z-Gu reversed the benefits of R.I on ICP rats. In conclusion, our research has identified R.I as a key player in ICP. We have demonstrated that R.I improved phenotypes associated with ICP through the bile acid/FXR-FGF15 signaling pathway. These findings suggested that R.I may be a promising target for the treatment of ICP. Our research highlights the important role of intestinal flora in the pathogenesis of ICP and provides a novel approach for its treatment. |
| 样品范围 |
Monoisolate |
| 发布日期 |
2023-12-29 |
| 出版信息 |
| PubMed ID |
文章标题 |
杂志名称 |
Doi |
发表年份 |
|
|
Roseburia intestinalis relieves intrahepatic cholestasis of pregnancy through bile acid/FXR-FGF15 in rats
|
iScience
|
10.1016/j.isci.2023.108392
|
2023
|
|
| 项目资金来源 |
| 机构 |
项目类型 |
授权项目ID |
授权项目名称 |
| No funding support
|
|
|
|
|
| 提交者 |
Hanxiang
Sun (shx10272023@163.com)
|
| 提交单位 |
Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University |
| 提交日期 |
2023-09-22 |