Alterations of gut microbiome in autoimmune hepatitis

Yiran Wei, Yanmei Li, Li Yan, Chunyan Sun, Qi Miao, Qixia Wang, Xiao Xiao, Min Lian, Bo Li, Yong Chen, Jun Zhang, You Li, Bingyuan Huang, Yikang Li, Qin Cao, Zhuping Fan, Xiaoyu Chen, Jing Yuan Fang, M. Eric Gershwin, Ruqi TangXiong Ma

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
JournalGut
DOIs
StatePublished - Jan 1 2019

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Autoimmune Hepatitis
Veillonella
Adrenal Cortex Hormones
Dysbiosis
Liver
Microbiota
Aspartate Aminotransferases
Gastrointestinal Microbiome
Autoimmunity
rRNA Genes
Area Under Curve
Lipopolysaccharides
Therapeutics
Cross-Sectional Studies
Biomarkers
Steroids
Inflammation
Bacteria
Amino Acids
Serum

Keywords

  • autoimmune hepatitis
  • intestinal microbiology

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Wei, Y., Li, Y., Yan, L., Sun, C., Miao, Q., Wang, Q., ... Ma, X. (2019). Alterations of gut microbiome in autoimmune hepatitis. Gut. https://doi.org/10.1136/gutjnl-2018-317836

Alterations of gut microbiome in autoimmune hepatitis. / Wei, Yiran; Li, Yanmei; Yan, Li; Sun, Chunyan; Miao, Qi; Wang, Qixia; Xiao, Xiao; Lian, Min; Li, Bo; Chen, Yong; Zhang, Jun; Li, You; Huang, Bingyuan; Li, Yikang; Cao, Qin; Fan, Zhuping; Chen, Xiaoyu; Fang, Jing Yuan; Gershwin, M. Eric; Tang, Ruqi; Ma, Xiong.

In: Gut, 01.01.2019.

Research output: Contribution to journalArticle

Wei, Y, Li, Y, Yan, L, Sun, C, Miao, Q, Wang, Q, Xiao, X, Lian, M, Li, B, Chen, Y, Zhang, J, Li, Y, Huang, B, Li, Y, Cao, Q, Fan, Z, Chen, X, Fang, JY, Gershwin, ME, Tang, R & Ma, X 2019, 'Alterations of gut microbiome in autoimmune hepatitis', Gut. https://doi.org/10.1136/gutjnl-2018-317836
Wei, Yiran ; Li, Yanmei ; Yan, Li ; Sun, Chunyan ; Miao, Qi ; Wang, Qixia ; Xiao, Xiao ; Lian, Min ; Li, Bo ; Chen, Yong ; Zhang, Jun ; Li, You ; Huang, Bingyuan ; Li, Yikang ; Cao, Qin ; Fan, Zhuping ; Chen, Xiaoyu ; Fang, Jing Yuan ; Gershwin, M. Eric ; Tang, Ruqi ; Ma, Xiong. / Alterations of gut microbiome in autoimmune hepatitis. In: Gut. 2019.
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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-na{\"i}ve 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-na{\"i}ve 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.",
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AU - Li, Yanmei

AU - Yan, Li

AU - Sun, Chunyan

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AU - Xiao, Xiao

AU - Lian, Min

AU - Li, Bo

AU - Chen, Yong

AU - Zhang, Jun

AU - Li, You

AU - Huang, Bingyuan

AU - Li, Yikang

AU - Cao, Qin

AU - Fan, Zhuping

AU - Chen, Xiaoyu

AU - Fang, Jing Yuan

AU - Gershwin, M. Eric

AU - Tang, Ruqi

AU - Ma, Xiong

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N2 - 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.

AB - 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.

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