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.

中文翻译：

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自身免疫性肝炎中肠道微生物组的改变

目的 肝脏-微生物组轴的重要性越来越被认为是自身免疫的主要调节剂。本研究的目的是利用大量明确定义的皮质类固醇治疗初治的自身免疫性肝炎 (AIH) 患者，与健康对照相比，严格表征肠道菌群失调。设计 我们通过 16S rRNA 基因测序对 AIH 患者 (n=91) 和匹配的健康对照 (n=98) 进行了横断面研究。分析了 28 名患者和 34 名对照的独立队列以验证结果。所有患者均在皮质类固醇治疗前收集。结果 类固醇治疗初治 AIH 的肠道微生物组具有较低的 α 多样性（香农和观察到的操作分类单位，均 p<0. 01) 和与健康对照相比明显的整体微生物组成 (p=0.002)。专性厌氧菌的消耗和包括韦永氏菌在内的潜在病原体的扩张与疾病状态有关。值得注意的是，与疾病相关性最强的分类群（p=8.85E-8）与血清天冬氨酸转氨酶水平和肝脏炎症呈正相关。此外，在探索和验证队列中，具有 AIH 相关属的四名患者的组合将 AIH 与对照组区分开来，曲线下面积约为 0.8。此外，AIH 肠道微生物组中的多个预测功能模块发生了改变，包括脂多糖生物合成以及可被细菌加工以产生免疫调节代谢物的氨基酸代谢。