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  • 1
    In: Gut, BMJ, Vol. 67, No. 3 ( 2018-03), p. 534-541
    Abstract: A close relationship between gut microbiota and some chronic liver disorders has recently been described. Herein, we systematically performed a comparative analysis of the gut microbiome in primary biliary cholangitis (PBC) and healthy controls. Design We first conducted a cross-sectional study of 60 ursodeoxycholic acid (UDCA) treatment-naïve patients with PBC and 80 matched healthy controls. Second, an independent cohort composed of 19 treatment-naïve patients and 34 controls was used to validate the results. Finally, a prospective study was performed in a subgroup of 37 patients with PBC who underwent analysis before and after 6 months of UDCA treatment. Faecal samples were collected, and microbiomes were analysed by 16S ribosomal RNA gene sequencing. Results A significant reduction of within-individual microbial diversity was noted in PBC (p=0.03). A signature defined by decreased abundance of four genera and increased abundance of eight genera strongly correlated with PBC (area under curve=0.86, 0.84 in exploration and validation data, respectively). Notably, the abundance of six PBC-associated genera was reversed after 6 months of UDCA treatment. In particular, Faecalibacterium , enriched in controls, was further decreased in gp210-positive than gp210-negative patients (p=0.002). Of interest was the finding that the increased capacity for the inferred pathway, bacterial invasion of epithelial cells in PBC, highly correlated with the abundance of bacteria belonging to Enterobacteriaceae . Conclusions This study presents a comprehensive landscape of gut microbiota in PBC. Dysbiosis was found in the gut microbiome in PBC and partially relieved by UDCA. Our study suggests that gut microbiota is a potential therapeutic target and diagnostic biomarker for PBC.
    Type of Medium: Online Resource
    ISSN: 0017-5749 , 1468-3288
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2018
    detail.hit.zdb_id: 1492637-4
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  • 2
    In: Gut, BMJ, Vol. 69, No. 3 ( 2020-03), p. 569-577
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0017-5749 , 1468-3288
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1492637-4
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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