Accession |
PRJCA020045 |
Title |
Roseburia intestinalis relieves intrahepatic cholestasis of pregnancy through bile acid/FXR-FGF15 in rats |
Relevance |
metabolomics |
Data types |
metabolomics
|
Organisms |
Rattus
|
Description |
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. |
Sample scope |
Monoisolate |
Release date |
2023-12-29 |
Publication |
PubMed ID |
Article title |
Journal name |
DOI |
Year |
|
Roseburia intestinalis relieves intrahepatic cholestasis of pregnancy through bile acid/FXR-FGF15 in rats
|
iScience
|
10.1016/j.isci.2023.108392
|
2023
|
|
Grants |
Agency |
program |
Grant ID |
Grant title |
No funding support
|
|
|
|
|
Submitter |
Hanxiang
Sun (shx10272023@163.com)
|
Organization |
Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University |
Submission date |
2023-09-22 |