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Comprehensive Analysis of Serum and Fecal Bile Acid Profiles and Interaction with Gut Microbiota in Primary Biliary Cholangitis.

Authors
  • Chen, Weihua1
  • Wei, Yiran1
  • Xiong, Aizhen2
  • Li, Yanmei1
  • Guan, Huida2
  • Wang, Qixia1
  • Miao, Qi1
  • Bian, Zhaolian3
  • Xiao, Xiao1
  • Lian, Min1
  • Zhang, Jun1
  • Li, Bo1
  • Cao, Qin4
  • Fan, Zhuping4
  • Zhang, Weici5
  • Qiu, Dekai1
  • Fang, Jingyuan1
  • Gershwin, M Eric5
  • Yang, Li6
  • Tang, Ruqi7
  • And 1 more
  • 1 Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001, China. , (China)
  • 2 The MOE Key Laboratory of Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. , (China)
  • 3 Nantong Institute of Liver Disease, Department of Gastroenterology and Hepatology, Nantong Third People's Hospital, Nantong University, 60 Middle Qingnian Road, Nantong, Jiangsu, China. , (China)
  • 4 Department of Health Manage Center, School of Medicine, RenJi Hospital, Shanghai Jiao Tong University, Shanghai, China. , (China)
  • 5 Division of Rheumatology, Department of Medicine, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA.
  • 6 The MOE Key Laboratory of Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. [email protected] , (China)
  • 7 Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001, China. [email protected] , (China)
  • 8 Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001, China. [email protected] , (China)
Type
Published Article
Journal
Clinical Reviews in Allergy & Immunology
Publisher
Springer-Verlag
Publication Date
Feb 01, 2020
Volume
58
Issue
1
Pages
25–38
Identifiers
DOI: 10.1007/s12016-019-08731-2
PMID: 30900136
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Accumulation of bile acids (BAs) contributes significantly to the pathogenesis of primary biliary cholangitis (PBC). Here, we sought to systematically characterize the serum and fecal BA profiles and the linkage between BAs and gut microbiota in PBC. The serum and fecal BAs were compared between 65 UDCA treatment-naive PBC and 109 healthy controls using UPLC-MS in cross-sectional study. In a prospective study, a subgroup of patients was enrolled for BA and microbiota analysis before and after UDCA therapy. BA compositions in serum and feces significantly differed between treatment-naive PBC and controls. Particularly, PBC was associated with decreased conversions of conjugated to unconjugated, and primary to secondary BAs, indicating impaired microbial metabolism of BAs. PBC patients at advanced stage exhibited a more abnormal BA profile compared with early-stage patients. UDCA treatment led to a decreased level of taurine-conjugated BAs, thereby reversing the conjugated/unconjugated ratio in PBC. Moreover, the level of secondary BAs such as DCA and conjugated DCA inversely correlated with PBC-enriched gut microbes (e.g., Veillonella, Klebsiella), while positively correlated with control-enriched microbes (e.g., Faecalibacterium, Oscillospira). Microbiota analysis also revealed a significant increase of taurine-metabolizing bacteria Bilophila spp. in patients after UDCA, which was strongly correlated with decreased taurine-conjugated BAs. In addition, serum FGF19 was remarkably increased in treatment-naïve PBC and decreased after UDCA. Our study established specific alterations of BA compositions in serum and feces of PBC, suggesting the potential for using BAs for diagnosis, and highlighting the possibility of modulating BA profile by altering gut microbiota. Graphical Abstract.

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