1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
European Reference Network for Hepatological Diseases (ERN-RARE-LIVER), Hamburg, Germany.
Aliment Pharmacol Ther. 2020 Jun;51(12):1417-1428. doi: 10.1111/apt.15754. Epub 2020 May 7.
The pathogenesis of autoimmune hepatitis (AIH) is poorly understood and little is known about enteric microbiota in AIH.
To investigate disease-specific microbiome alterations in AIH.
The V1-V2 variable regions of the 16S rRNA gene were sequenced in faecal samples from 347 patients with AIH and controls (AIH n = 72, healthy controls (HC) n = 95, primary biliary cholangitis (PBC) n = 99 and ulcerative colitis (UC) n = 81).
Biodiversity (Shannon entropy) was decreased in AIH patients compared to HC (P = 0.016), which was partially reversed by azathioprine (P = 0.011). Regarding between-sample diversity, AIH patients separated from HC, PBC and UC individuals (all P = 0.001). Compared to HC, decreased relative abundance of anaerobic genera such as Faecalibacterium and an increase of Veillonella and the facultative anaerobic genera Streptococcus and Lactobacillus were detected. Importantly, a disease-specific decline of relative abundance of Bifidobacterium was observed in AIH patients. Lack of Bifidobacterium was associated with failure to achieve remission of AIH (P < 0.001). Of potential therapeutic implication, Bifidobacterium abundance correlated with average protein intake (P < 0.001). Random forests classification between AIH and PBC on the microbiome signature yielded an area under receiver operating characteristic curve (AUC) of 0.787 in the training cohort, and an AUC of 0.849 in an external validation cohort.
Disease-specific faecal microbial alterations were identified in patients with AIH. Intestinal dysbiosis in AIH was characterised by a decline of Bifidobacterium, which was associated with increased disease activity. These results point to the contribution of intestinal microbiota to AIH pathogenesis and to novel therapeutic targets.
自身免疫性肝炎（AIH）的发病机制尚未完全阐明，对 AIH 中的肠道微生物群了解甚少。
研究 AIH 中特定疾病的微生物组改变。
对 347 名 AIH 患者和对照组（AIH n=72、健康对照组（HC）n=95、原发性胆汁性胆管炎（PBC）n=99 和溃疡性结肠炎（UC）n=81）的粪便样本进行 16S rRNA 基因 V1-V2 可变区测序。
与 HC 相比，AIH 患者的生物多样性（Shannon 熵）降低（P=0.016），而这一结果在接受硫唑嘌呤治疗后部分逆转（P=0.011）。关于样本间的多样性，AIH 患者与 HC、PBC 和 UC 个体分开（均 P=0.001）。与 HC 相比，检测到厌氧属（如 Faecalibacterium）的相对丰度降低，兼性厌氧菌属（如 Veillonella、Streptococcus 和 Lactobacillus）的相对丰度增加。重要的是，在 AIH 患者中观察到双歧杆菌相对丰度的特异性下降。双歧杆菌缺乏与 AIH 无法缓解有关（P<0.001）。双歧杆菌丰度与平均蛋白质摄入量相关（P<0.001），具有潜在的治疗意义。基于微生物组特征对 AIH 和 PBC 进行随机森林分类，在训练队列中的受试者工作特征曲线（ROC）下面积（AUC）为 0.787，在外部验证队列中的 AUC 为 0.849。
在 AIH 患者中发现了特定疾病的粪便微生物改变。AIH 中的肠道菌群失调表现为双歧杆菌的减少，这与疾病活动增加有关。这些结果表明肠道微生物群对 AIH 发病机制的贡献，并为新的治疗靶点提供了依据。
