Alterations of gut microbiome in autoimmune hepatitis

Study information

Reviewed Marked as Reviewed by Atrayees on 2023-7-19

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

31201284

DOI Digital object identifier for electronic documents.

10.1136/gutjnl-2018-317836

URI

Authors

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

Journal

Gut

Year

2020

Keywords:

autoimmune hepatitis, intestinal microbiology

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.

Experiment 1

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Reviewed Marked as Reviewed by Atrayees on 2023-7-19

Curated date: 2021/02/24

Curator: Valentina

Revision editor(s): Valentina, WikiWorks, Atrayees, Peace Sandy

Subjects

Location of subjects: China

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Autoimmune Hepatitis AIH,autoimmune chronic active hepatitis,autoimmune chronic hepatitis,autoimmune hepatitis,autoimmune hepatitis with centrilobular necrosis,autoimmune liver disease,autoimmune-like hepatitis,chronic autoimmune hepatitis,Autoimmune Hepatitis,autoimmune Hepatitis

Group 0 name Corresponds to the control (unexposed) group for case-control studies: healthy controls

Group 1 name Corresponds to the case (exposed) group for case-control studies: autoimmune hepatits cases

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: The diagnosis of AIH was made if patients conformed with (1) 1999 revised International Autoimmune Hepatitis Group (IAIHG) score ≥10 and/or (2) 2008 IAIHG simplified AIH score ≥6 and/or (3) histological features indicative of AIH.

Group 0 sample size Number of subjects in the control (unexposed) group: 98

Group 1 sample size Number of subjects in the case (exposed) group: 91

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 4 weeks

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3-V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: No

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 2.0

Matched on Factors on which subjects have been matched on in a case-control study: age, body mass index, sex

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: age, body mass index, antibiotic exposure, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: decreased

Richness Number of species: decreased

Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample: decreased

Signature 1

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Curated date: 2021/02/25

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Source: Figure 2

Description: LDA effect size analysis of 11 genera was significantly different between AIH and the control group.

Abundance in Group 1: increased abundance in autoimmune hepatits cases

NCBI	Quality Control	Links
Klebsiella
Lactobacillus
Streptococcus
Veillonella

Revision editor(s): Valentina

Signature 2

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Curated date: 2021/03/03

Curator: Valentina

Revision editor(s): Valentina, Atrayees

Source: Figure 2

Description: LDA effect size analysis of taxa that was significantly different between AIH and the control group.

Abundance in Group 1: decreased abundance in autoimmune hepatits cases

NCBI	Quality Control	Links
Coprococcus
Oscillospira
Parabacteroides
Rikenellaceae
Oscillospiraceae

Revision editor(s): Valentina, Atrayees

Experiment 2

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Reviewed Marked as Reviewed by Atrayees on 2023-7-19

Curated date: 2021/03/03

Curator: Valentina

Revision editor(s): Fatima, Valentina, WikiWorks

Differences from previous experiment shown

Subjects

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): Not specified

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: Not specified