Clostridium Scindens Protects Against Vancomycin‐Induced Cholestasis and Liver Fibrosis by Activating Intestinal FXR‐FGF15/19 Signaling
Abstract Primary sclerosing cholangitis (PSC) is characterized by abnormal bile acid metabolites and altered gut microbiota, with no effective treatments available. Vancomycin, a glycopeptide antibiotic, has emerged as a promising candidate. However, the mechanism by which vancomycin impacts the pro...
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| Format: | Article |
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Wiley
2025-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202406445 |
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| author | Jintao Xiao Yanliang Hou Xingyang Luo Yuhao Zhu Wenhu Li Bingbing Li LinXiang Zhou Xia Chen Ying Guo Xiaomei Zhang Haiyue He Xiaowei Liu |
| author_facet | Jintao Xiao Yanliang Hou Xingyang Luo Yuhao Zhu Wenhu Li Bingbing Li LinXiang Zhou Xia Chen Ying Guo Xiaomei Zhang Haiyue He Xiaowei Liu |
| author_sort | Jintao Xiao |
| collection | DOAJ |
| description | Abstract Primary sclerosing cholangitis (PSC) is characterized by abnormal bile acid metabolites and altered gut microbiota, with no effective treatments available. Vancomycin, a glycopeptide antibiotic, has emerged as a promising candidate. However, the mechanism by which vancomycin impacts the progression of PSC remains unknown. Mice treated with vancomycin exhibit increased hepatic collagen deposition and injury, due to the inhibition of intestinal FXR‐FGF15/19 axis and the elevation of bile acid levels. These effects are associated with the reduction in Clostridia XIVa, especially Clostridium scindens (C. scindens). Gavage of C. scindens alleviates vancomycin‐induced bile acid accumulation and liver fibrosis via activating intestinal FXR‐FGF15/19 signaling. Similar effects are observed in mice treated with engineered Escherichia coli Nissle 1917 that are capable of expressing bile acid 7α‐dehydratas (BaiE) from C. scindens (EcN‐BaiE). Activating intestinal FXR‐FGF15/19 signaling by fexaramine (Fex) or recombinant protein FGF19 reverse vancomycin‐induced liver injury and fibrosis. These results demonstrate that long‐term oral vancomycin exacerbates cholestatic liver injury, while C. scindens mitigates this effect by activating the intestinal FXR‐FGF15/19 signaling pathway. This underscores the importance of monitoring bile acid levels in PSC patients receiving vancomycin treatment and suggests that C. scindens may serve as a potential therapeutic approach for PSC patients. |
| format | Article |
| id | doaj-art-f8984f9e0a674d39a9c1bc9b329f1f0f |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-f8984f9e0a674d39a9c1bc9b329f1f0f2025-02-04T13:14:54ZengWileyAdvanced Science2198-38442025-02-01125n/an/a10.1002/advs.202406445Clostridium Scindens Protects Against Vancomycin‐Induced Cholestasis and Liver Fibrosis by Activating Intestinal FXR‐FGF15/19 SignalingJintao Xiao0Yanliang Hou1Xingyang Luo2Yuhao Zhu3Wenhu Li4Bingbing Li5LinXiang Zhou6Xia Chen7Ying Guo8Xiaomei Zhang9Haiyue He10Xiaowei Liu11Department of Gastroenterology Xiangya Hospital Central South University Changsha Hunan 410008 ChinaDepartment of Gastroenterology Xiangya Hospital Central South University Changsha Hunan 410008 ChinaDepartment of Gastroenterology Xiangya Hospital Central South University Changsha Hunan 410008 ChinaDepartment of Gastroenterology Xiangya Hospital Central South University Changsha Hunan 410008 ChinaDepartment of Gastroenterology Xiangya Hospital Central South University Changsha Hunan 410008 ChinaDepartment of Gastroenterology Xiangya Hospital Central South University Changsha Hunan 410008 ChinaDepartment of Gastroenterology Xiangya Hospital Central South University Changsha Hunan 410008 ChinaDepartment of Clinical Laboratory Xiangya Hospital Central South University Changsha Hunan 410008 ChinaDepartment of Clinical Pharmacology Xiangya Hospital Hunan Key Laboratory of Pharmacogenetics Central South University Changsha Hunan 410008 ChinaDepartment of Gastroenterology Xiangya Hospital Central South University Changsha Hunan 410008 ChinaDepartment of Gastroenterology Xiangya Hospital Central South University Changsha Hunan 410008 ChinaDepartment of Gastroenterology Xiangya Hospital Central South University Changsha Hunan 410008 ChinaAbstract Primary sclerosing cholangitis (PSC) is characterized by abnormal bile acid metabolites and altered gut microbiota, with no effective treatments available. Vancomycin, a glycopeptide antibiotic, has emerged as a promising candidate. However, the mechanism by which vancomycin impacts the progression of PSC remains unknown. Mice treated with vancomycin exhibit increased hepatic collagen deposition and injury, due to the inhibition of intestinal FXR‐FGF15/19 axis and the elevation of bile acid levels. These effects are associated with the reduction in Clostridia XIVa, especially Clostridium scindens (C. scindens). Gavage of C. scindens alleviates vancomycin‐induced bile acid accumulation and liver fibrosis via activating intestinal FXR‐FGF15/19 signaling. Similar effects are observed in mice treated with engineered Escherichia coli Nissle 1917 that are capable of expressing bile acid 7α‐dehydratas (BaiE) from C. scindens (EcN‐BaiE). Activating intestinal FXR‐FGF15/19 signaling by fexaramine (Fex) or recombinant protein FGF19 reverse vancomycin‐induced liver injury and fibrosis. These results demonstrate that long‐term oral vancomycin exacerbates cholestatic liver injury, while C. scindens mitigates this effect by activating the intestinal FXR‐FGF15/19 signaling pathway. This underscores the importance of monitoring bile acid levels in PSC patients receiving vancomycin treatment and suggests that C. scindens may serve as a potential therapeutic approach for PSC patients.https://doi.org/10.1002/advs.202406445cholestatic liver diseasesClostridium scindensFXR‐FGF15/19 signalinggut microbiotaliver fibrosisvancomycin |
| spellingShingle | Jintao Xiao Yanliang Hou Xingyang Luo Yuhao Zhu Wenhu Li Bingbing Li LinXiang Zhou Xia Chen Ying Guo Xiaomei Zhang Haiyue He Xiaowei Liu Clostridium Scindens Protects Against Vancomycin‐Induced Cholestasis and Liver Fibrosis by Activating Intestinal FXR‐FGF15/19 Signaling Advanced Science cholestatic liver diseases Clostridium scindens FXR‐FGF15/19 signaling gut microbiota liver fibrosis vancomycin |
| title | Clostridium Scindens Protects Against Vancomycin‐Induced Cholestasis and Liver Fibrosis by Activating Intestinal FXR‐FGF15/19 Signaling |
| title_full | Clostridium Scindens Protects Against Vancomycin‐Induced Cholestasis and Liver Fibrosis by Activating Intestinal FXR‐FGF15/19 Signaling |
| title_fullStr | Clostridium Scindens Protects Against Vancomycin‐Induced Cholestasis and Liver Fibrosis by Activating Intestinal FXR‐FGF15/19 Signaling |
| title_full_unstemmed | Clostridium Scindens Protects Against Vancomycin‐Induced Cholestasis and Liver Fibrosis by Activating Intestinal FXR‐FGF15/19 Signaling |
| title_short | Clostridium Scindens Protects Against Vancomycin‐Induced Cholestasis and Liver Fibrosis by Activating Intestinal FXR‐FGF15/19 Signaling |
| title_sort | clostridium scindens protects against vancomycin induced cholestasis and liver fibrosis by activating intestinal fxr fgf15 19 signaling |
| topic | cholestatic liver diseases Clostridium scindens FXR‐FGF15/19 signaling gut microbiota liver fibrosis vancomycin |
| url | https://doi.org/10.1002/advs.202406445 |
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