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

  • Weihua Chen
  • Yiran Wei
  • Aizhen Xiong
  • Yanmei Li
  • Huida Guan
  • Qixia Wang
  • Qi Miao
  • Zhaolian Bian
  • Xiao Xiao
  • Min Lian
  • Jun Zhang
  • Bo Li
  • Qin Cao
  • Zhuping Fan
  • Weici Zhang
  • Dekai Qiu
  • Jingyuan Fang
  • M. Eric Gershwin
  • Li YangEmail author
  • Ruqi TangEmail author
  • Xiong MaEmail author


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


Primary biliary cholangitis Bile acids Gut microbiota Ursodeoxycholic acid 



Primary biliary cholangitis


Ursodeoxycholic acid


Bile acid


Cholic acid


Taurocholic acid


Glycocholic acid


Deoxycholic acid


Taurodeoxycholic acid


Glycodeoxycholic acid


Chenodeoxycholic acid


Taurochenodeoxycholic acid


Glycochenodeoxycholic acid


Tauroursodeoxycholic acid


Glycoursodeoxycholic acid


Hyodeoxycholic acid


Taurohyodeoxycholic acid


Lithocholic acid


Taurolithocholic acid


Ultra-performance liquid chromatography/mass spectrometry


Bile salt hydrolase


Cholesterol 7α-hydroxylase


Farnesoid X receptor


Fibroblast growth factor 19


Alkline phosphatase


γ-Glutamyl transferase


Alanine aminotransferase


Aspartate transaminase


Immunoglobulin M


Upper limit of normal


Body mass index


Generalized estimated equation


False discovery rate



We are grateful for all the subjects who participated in the study.

Financial Support

This work was supported by the National Natural Science Foundation of China grants (#81620108002, 81771732, and 81830016 to XM, # 81570469 and 81873561 to RT, #81573581 to LY, #81421001 to JF, #81500435 to XX) and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (#20161311 to RT).

Author Contributions

XM, RT, LY, and MEG designed and supervised the project; XM, RT, LY, and JF obtained funding. QW, ML, QM, and DQ performed clinical diagnosis and treatment. WC, YW, YL, BL, ZB, QC, and PF collected samples. YW, YL, AX, HG, and JZ contributed to data collection. YW, YL, and WC performed the experiments. RT, YW, YL, and AX performed bioinformatics and statistical analysis; interpreted data. RT, YW, and WC drafted the manuscript. WZ, XM, MEG, and LY revised the manuscript for important content.

Compliance with Ethical Standards

Competing Interests

None declared.

Supplementary material

12016_2019_8731_MOESM1_ESM.pdf (7.5 mb)
ESM 1 (PDF 7660 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Weihua Chen
    • 1
  • Yiran Wei
    • 1
  • Aizhen Xiong
    • 2
  • Yanmei Li
    • 1
  • Huida Guan
    • 2
  • Qixia Wang
    • 1
  • Qi Miao
    • 1
  • Zhaolian Bian
    • 3
  • Xiao Xiao
    • 1
  • Min Lian
    • 1
  • Jun Zhang
    • 1
  • Bo Li
    • 1
  • Qin Cao
    • 4
  • Zhuping Fan
    • 4
  • Weici Zhang
    • 5
  • Dekai Qiu
    • 1
  • Jingyuan Fang
    • 1
  • M. Eric Gershwin
    • 5
  • Li Yang
    • 2
    Email author
  • Ruqi Tang
    • 1
    Email author
  • Xiong Ma
    • 1
    Email author
  1. 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 UniversityShanghai Institute of Digestive DiseaseShanghaiChina
  2. 2.The MOE Key Laboratory of Standardization of Chinese Medicines, Institute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghaiChina
  3. 3.Nantong Institute of Liver Disease, Department of Gastroenterology and Hepatology, Nantong Third People’s HospitalNantong UniversityNantongChina
  4. 4.Department of Health Manage Center, School of Medicine, RenJi HospitalShanghai Jiao Tong UniversityShanghaiChina
  5. 5.Division of Rheumatology, Department of Medicine, Allergy and Clinical ImmunologyUniversity of California at DavisDavisUSA

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