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
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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.
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