Discovery biomarker to optimize obeticholic acid treatment for non-alcoholic fatty liver disease
Abstract The response rate to obeticholic acid (OCA), a potential therapeutic agent for non-alcoholic fatty liver disease, is limited. This study demonstrated that upregulation of the alternative bile acid synthesis pathway increases the OCA treatment response rate. The hepatic transcriptome and bil...
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | Biology Direct |
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| Online Access: | https://doi.org/10.1186/s13062-023-00407-4 |
| _version_ | 1797577540394549248 |
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| author | Seung Min Lee Dae Won Jun Eileen Laurel Yoon Ju Hee Oh Yoon Jin Roh Eun Jeoung Lee Ji-Hee Shin Young-Do Nam Hyun Sung Kim |
| author_facet | Seung Min Lee Dae Won Jun Eileen Laurel Yoon Ju Hee Oh Yoon Jin Roh Eun Jeoung Lee Ji-Hee Shin Young-Do Nam Hyun Sung Kim |
| author_sort | Seung Min Lee |
| collection | DOAJ |
| description | Abstract The response rate to obeticholic acid (OCA), a potential therapeutic agent for non-alcoholic fatty liver disease, is limited. This study demonstrated that upregulation of the alternative bile acid synthesis pathway increases the OCA treatment response rate. The hepatic transcriptome and bile acid metabolite profile analyses revealed that the alternative bile acid synthesis pathway (Cyp7b1 and muricholic acid) in the OCA-responder group were upregulated compared with those in the OCA-non-responder group. Intestinal microbiome analysis also revealed that the abundances of Bacteroidaceae, Parabacteroides, and Bacteroides, which were positively correlated with the alternative bile acid synthesis pathway, were higher in the OCA-responder group than in the non-responder group. Pre-study hepatic mRNA levels of Cyp8b1 (classic pathway) were downregulated in the OCA-responder group. The OCA response rate increased up to 80% in cases with a hepatic Cyp7b1/Cyp8b1 ratio ≥ 5.0. Therefore, the OCA therapeutic response can be evaluated based on the Cyp7b1/Cyp8b1 ratio or the alternative/classic bile acid synthesis pathway activity. |
| first_indexed | 2024-03-10T22:10:44Z |
| format | Article |
| id | doaj.art-dcdb94efdec346ec83a896b3e8f7dcda |
| institution | Directory Open Access Journal |
| issn | 1745-6150 |
| language | English |
| last_indexed | 2024-03-10T22:10:44Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology Direct |
| spelling | doaj.art-dcdb94efdec346ec83a896b3e8f7dcda2023-11-19T12:38:28ZengBMCBiology Direct1745-61502023-08-0118111210.1186/s13062-023-00407-4Discovery biomarker to optimize obeticholic acid treatment for non-alcoholic fatty liver diseaseSeung Min Lee0Dae Won Jun1Eileen Laurel Yoon2Ju Hee Oh3Yoon Jin Roh4Eun Jeoung Lee5Ji-Hee Shin6Young-Do Nam7Hyun Sung Kim8Department of Translational Medicine, Graduate School of Biomedical Science & Engineering, Hanyang UniversityDepartment of Translational Medicine, Graduate School of Biomedical Science & Engineering, Hanyang UniversityDepartment of Internal Medicine, Hanyang University Hospital, Hanyang University College of MedicineDepartment of Obstetrics and Gynecology, Institute of Women’s Medical Life Science, Severance Hospital, Yonsei Cancer Center, Yonsei University College of MedicineDepartment of Dermatology, Chung-Ang University HospitalDepartment of Translational Medicine, Graduate School of Biomedical Science & Engineering, Hanyang UniversityResearch Group of Personalized Diet, Korea Food Research InstituteResearch Group of Personalized Diet, Korea Food Research InstitutePathology, Medical genetic, Hanyang University College of MedicineAbstract The response rate to obeticholic acid (OCA), a potential therapeutic agent for non-alcoholic fatty liver disease, is limited. This study demonstrated that upregulation of the alternative bile acid synthesis pathway increases the OCA treatment response rate. The hepatic transcriptome and bile acid metabolite profile analyses revealed that the alternative bile acid synthesis pathway (Cyp7b1 and muricholic acid) in the OCA-responder group were upregulated compared with those in the OCA-non-responder group. Intestinal microbiome analysis also revealed that the abundances of Bacteroidaceae, Parabacteroides, and Bacteroides, which were positively correlated with the alternative bile acid synthesis pathway, were higher in the OCA-responder group than in the non-responder group. Pre-study hepatic mRNA levels of Cyp8b1 (classic pathway) were downregulated in the OCA-responder group. The OCA response rate increased up to 80% in cases with a hepatic Cyp7b1/Cyp8b1 ratio ≥ 5.0. Therefore, the OCA therapeutic response can be evaluated based on the Cyp7b1/Cyp8b1 ratio or the alternative/classic bile acid synthesis pathway activity.https://doi.org/10.1186/s13062-023-00407-4Non-alcoholic fatty liverObeticholic acidBile acidAlternative pathwayBiomarkerMicrobiome |
| spellingShingle | Seung Min Lee Dae Won Jun Eileen Laurel Yoon Ju Hee Oh Yoon Jin Roh Eun Jeoung Lee Ji-Hee Shin Young-Do Nam Hyun Sung Kim Discovery biomarker to optimize obeticholic acid treatment for non-alcoholic fatty liver disease Biology Direct Non-alcoholic fatty liver Obeticholic acid Bile acid Alternative pathway Biomarker Microbiome |
| title | Discovery biomarker to optimize obeticholic acid treatment for non-alcoholic fatty liver disease |
| title_full | Discovery biomarker to optimize obeticholic acid treatment for non-alcoholic fatty liver disease |
| title_fullStr | Discovery biomarker to optimize obeticholic acid treatment for non-alcoholic fatty liver disease |
| title_full_unstemmed | Discovery biomarker to optimize obeticholic acid treatment for non-alcoholic fatty liver disease |
| title_short | Discovery biomarker to optimize obeticholic acid treatment for non-alcoholic fatty liver disease |
| title_sort | discovery biomarker to optimize obeticholic acid treatment for non alcoholic fatty liver disease |
| topic | Non-alcoholic fatty liver Obeticholic acid Bile acid Alternative pathway Biomarker Microbiome |
| url | https://doi.org/10.1186/s13062-023-00407-4 |
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