Biotransformation of chenodeoxycholic acid by human intestinal fungi and the agonistic effects on FXR.

Chenodeoxycholic acid FXR biotransformation intestinal fungi

Journal

Phytochemistry
ISSN: 1873-3700
Titre abrégé: Phytochemistry
Pays: England
ID NLM: 0151434

Informations de publication

Date de publication:
24 May 2024
Historique:
received: 20 02 2024
revised: 13 05 2024
accepted: 24 05 2024
medline: 27 5 2024
pubmed: 27 5 2024
entrez: 26 5 2024
Statut: aheadofprint

Résumé

Bile acids play a vital role in modulating host metabolism, with chenodeoxycholic acid (CDCA) standing out as a primary bile acid that naturally activates farnesoid X receptor (FXR). In this study, we investigated the microbial transformations of CDCA by seven human intestinal fungal species. Our findings revealed that hydroxylation and dehydrogenation were the most prevalent metabolic pathways. Incubation of CDCA with Rhizopus microspores (PT2906) afforded eight undescribed compounds (6-13) alongside five known analogs (1-5) which were elucidated by HRESI-MS and NMR data. Notably, compounds 8, 12 and 13 exhibited an inhibitory effect on FXR in contrast to the FXR activation observed with CDCA in vitro assays. This study shone a light on the diverse transformations of CDCA by intestinal fungi, unveiling potential modulators of FXR activity with implications for host metabolism.

Identifiants

DOI: 10.1016/j.phytochem.2024.114162 PMID: 38797255
pubmed: 38797255
pii: S0031-9422(24)00199-7
doi: 10.1016/j.phytochem.2024.114162
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

114162

Informations de copyright

Copyright © 2024. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:

Auteurs

Xuemei Wei (X)

National Engineering Research Center of TCM Standardization Technology, Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmaceutical Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.

Changliang Yao (C)

National Engineering Research Center of TCM Standardization Technology, Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Xin He (X)

National Engineering Research Center of TCM Standardization Technology, Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Jiayuan Li (J)

National Engineering Research Center of TCM Standardization Technology, Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Yulu Wang (Y)

National Engineering Research Center of TCM Standardization Technology, Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Chao Wang (C)

College of Integrative Medicine, College of Pharmacy, Dalian Medical University, Dalian 116044, China.

Qinhua Chen (Q)

Shenzhen Baoan Authentic TCM Therapy Hospital, Shenzhen 518101, China.

Xiaochi Ma (X)

College of Integrative Medicine, College of Pharmacy, Dalian Medical University, Dalian 116044, China. Electronic address: maxc1978@163.com.

De-An Guo (DA)

National Engineering Research Center of TCM Standardization Technology, Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmaceutical Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China. Electronic address: daguo@simm.ac.cn.

Classifications MeSH