Pereira Pedro, Aho Velma, Arola Johanna, Boyd Sonja, Jokelainen Kalle, Paulin Lars, Auvinen Petri, Färkkilä Martti
Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
University of Helsinki, Department of Pathology, Helsinki University Hospital, Helsinki, Finland.
PLoS One. 2017 Aug 10;12(8):e0182924. doi: 10.1371/journal.pone.0182924. eCollection 2017.
The etiopathogenesis and risk for development of biliary neoplasia in primary sclerosing cholangitis (PSC) are largely unknown. Microbes or their metabolites have been suggested to play a role. To explore this potential microbial involvement, we evaluated the differences in biliary microbiota in PSC patients at an early disease stage without previous endoscopic retrograde cholangiography (ERC) examinations, advanced disease stage, and with biliary dysplasia or cholangiocarcinoma.
Bile samples from the common bile duct were collected from 46 controls and 80 patients with PSC during ERC (37 with early disease, 32 with advanced disease, and 11 with biliary dysplasia). DNA isolation, amplification, and Illumina MiSeq sequencing were performed for the V1-V3 regions of the bacterial 16S rRNA gene.
The most common phyla found were Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria, and Actinobacteria. The most common families were Prevotellaceae, Streptococcaceae, Veillonellaceae, Fusobacteriaceae, and Pasteurellaceae, and the most common genera were Prevotella, Streptococcus, Veillonella, Fusobacterium, and Haemophilus. The bacterial communities of non-PSC subjects and early stage PSC patients were similar. Alpha diversity was lower in patients with biliary dysplasia/cholangiocarcinoma than in other groups. An increase in Streptococcus abundance was positively correlated with the number of ERC examinations. Streptococcus abundance was also positively correlated with an increase in disease severity, even after controlling for the number of ERC examinations.
Our findings suggest that the aetiology of PSC is not associated with changes in bile microbial communities, but the genus Streptococcus may play a pathogenic role in the progression of the disease.
原发性硬化性胆管炎（PSC）中胆管肿瘤形成的病因和风险在很大程度上尚不清楚。有研究表明微生物或其代谢产物可能起作用。为探究这种潜在的微生物参与情况，我们评估了处于疾病早期且未进行过先前内镜逆行胆管造影（ERC）检查的PSC患者、疾病晚期患者以及伴有胆管发育异常或胆管癌患者的胆汁微生物群差异。
在ERC期间从46名对照者和80名PSC患者的胆总管采集胆汁样本（37例疾病早期患者、32例疾病晚期患者和11例胆管发育异常患者）。对细菌16S rRNA基因的V1 - V3区域进行DNA分离、扩增和Illumina MiSeq测序。
发现最常见的门为拟杆菌门、厚壁菌门、变形菌门、梭杆菌门和放线菌门。最常见的科为普雷沃氏菌科、链球菌科、韦荣氏菌科、梭杆菌科和巴斯德菌科，最常见的属为普雷沃氏菌属、链球菌属、韦荣氏菌属、梭杆菌属和嗜血杆菌属。非PSC受试者和早期PSC患者的细菌群落相似。胆管发育异常/胆管癌患者的α多样性低于其他组。链球菌丰度的增加与ERC检查次数呈正相关。即使在控制了ERC检查次数后，链球菌丰度也与疾病严重程度的增加呈正相关。
我们的研究结果表明，PSC的病因与胆汁微生物群落的变化无关，但链球菌属可能在疾病进展中起致病作用。
