Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy
Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy
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原发性胆汁性胆管炎肠道微生物特征发生改变，UDCA 治疗后部分恢复
DOI：
10.1136/gutjnl-2016-313332
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发表时间：
2018-03-01
期刊：
影响因子：
24.5
通讯作者：
Ma, Xiong
中科院分区：
文献类型：
--
作者：
Tang, Ruqi;Wei, Yiran;Ma, Xiong
目的肠道菌群与某些慢性肝病的关系日益密切。在此，我们系统地对原发性胆管炎（PBC）和健康对照组的肠道微生物组进行了比较分析。设计我们首先对60例熊去氧胆酸（UDCA）治疗初治的PBC患者和80例匹配的健康对照进行了横断面研究。第二，使用由19名未经治疗的患者和34名对照组成的独立队列来验证结果。最后，在37例PBC患者的亚组中进行了一项前瞻性研究，这些患者在UDCA治疗6个月前后进行了分析。 收集粪便样本，并通过16S核糖体RNA基因测序分析微生物组。结果PBC患者个体内微生物多样性显著降低（p=0.03）。由四个属的丰度减少和八个属的丰度增加定义的签名与PBC强烈相关（在勘探和验证数据中，曲线下的面积分别为0.86，0.84）。值得注意的是，UDCA治疗6个月后，6种PBC相关属的丰度发生逆转。 特别地，在对照中富集的粪杆菌在gp210阳性患者中比gp210阴性患者进一步减少（p=0.002）。令人感兴趣的是，发现推断途径的能力增加，PBC中上皮细胞的细菌侵入，与属于肠杆菌科的细菌的丰度高度相关。结论本研究提供了PBC患者肠道菌群的全面景观。PBC的肠道微生物组中发现了生态失调，UDCA部分缓解了这种情况。我们的研究表明，肠道微生物群是PBC的潜在治疗靶点和诊断生物标志物。
Objective 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.