Article Text

Download PDFPDF
Original article
Alterations of gut microbiome in autoimmune hepatitis
  1. Yiran Wei1,
  2. Yanmei Li1,
  3. Li Yan1,
  4. Chunyan Sun1,
  5. Qi Miao1,
  6. Qixia Wang1,
  7. Xiao Xiao1,
  8. Min Lian1,
  9. Bo Li1,
  10. Yong Chen1,
  11. Jun Zhang1,
  12. You Li1,
  13. Bingyuan Huang1,
  14. Yikang Li1,
  15. Qin Cao2,
  16. Zhuping Fan2,
  17. Xiaoyu Chen1,
  18. Jing-Yuan Fang1,
  19. Merrill Eric Gershwin3,
  20. Ruqi Tang1,
  21. Xiong Ma1
  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 University; Shanghai Institute of Digestive Disease, Shanghai, China
  2. 2 Department of Health Manage Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  3. 3 Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, California, USA
  1. Correspondence to Dr Ruqi Tang and Professor Xiong Ma, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China; ruqi.tang{at}gmail.com, maxiongmd{at}hotmail.com

Abstract

Objective The significance of the liver-microbiome axis has been increasingly recognised as a major modulator of autoimmunity. The aim of this study was to take advantage of a large well-defined corticosteroids treatment-naïve group of patients with autoimmune hepatitis (AIH) to rigorously characterise gut dysbiosis compared with healthy controls.

Design We performed a cross-sectional study of individuals with AIH (n=91) and matched healthy controls (n=98) by 16S rRNA gene sequencing. An independent cohort of 28 patients and 34 controls was analysed to validate the results. All the patients were collected before corticosteroids therapy.

Results The gut microbiome of steroid treatment-naïve AIH was characterised with lower alpha-diversity (Shannon and observed operational taxonomic units, both p<0.01) and distinct overall microbial composition compared with healthy controls (p=0.002). Depletion of obligate anaerobes and expansion of potential pathobionts including Veillonella were associated with disease status. Of note, Veillonella dispar, the most strongly disease-associated taxa (p=8.85E–8), positively correlated with serum level of aspartate aminotransferase and liver inflammation. Furthermore, the combination of four patients with AIH-associated genera distinguished AIH from controls with an area under curves of approximately 0.8 in both exploration and validation cohorts. In addition, multiple predicted functional modules were altered in the AIH gut microbiome, including lipopolysaccharide biosynthesis as well as metabolism of amino acids that can be processed by bacteria to produce immunomodulatory metabolites.

Conclusion Our study establishes compositional and functional alterations of gut microbiome in AIH and suggests the potential for using gut microbiota as non-invasive biomarkers to assess disease activity.

  • autoimmune hepatitis
  • intestinal microbiology
View Full Text

Statistics from Altmetric.com

Footnotes

  • YW, YL, LY and CS share joint first co-authorship.

  • Contributors XM, RT and MEG conceived and designed the project. XM, J-YF, RT and QW obtained funding. QM, XC, QW and XX performed clinical diagnosis. YW, YL, LY, CS, YC, BL, ML, JZ, YL, BH, QC and ZF collected samples. YW, YL, LY and CS contributed to data collection. RT, YW and YL analysed and interpreted data. RT and YW drafted the manuscript. XM and MEG revised the manuscript. All the authors approved the final version of the manuscript.

  • Funding This work was supported by the National Natural Science Foundation of China grants (#81620108002, 81771732 and 81830016 to XM, #81570469 and 81873561 to RT, #81421001 to J-YF, #81790634 to QW), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (#20161311 to RT) and ‘Shuguang Program’ supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission (#18SG17 to RT).

  • Competing interests None declared.

  • Ethics approval Renji Hospital, School of Medicine, Shanghai Jiao Tong University (#2013-030).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Correction notice This article has been corrected since it published Online First. The joint authorship statement has been added.

  • Patient consent for publication Obtained.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.