PDF(Pubmed)
Abstract：
Pancreatic ductal adenocarcinoma (PDAC) has a very poor survival. The intra-tumoural microbiome can influence pancreatic tumourigenesis and chemoresistance and, therefore, patient survival. The role played by bile microbiota in PDAC is unknown. We aimed to define bile microbiome signatures that can effectively distinguish malignant from benign tumours in patients presenting with obstructive jaundice caused by benign and malignant pancreaticobiliary disease. Prospective bile samples were obtained from 31 patients who underwent either Endoscopic Retrograde Cholangiopancreatography (ERCP) or Percutaneous Transhepatic Cholangiogram (PTC). Variable regions (V3-V4) of the 16S rRNA genes of microorganisms present in the samples were amplified by Polymerase Chain Reaction (PCR) and sequenced. The cohort consisted of 12 PDAC, 10 choledocholithiasis, seven gallstone pancreatitis and two primary sclerosing cholangitis patients. Using the 16S rRNA method, we identified a total of 135 genera from 29 individuals (12 PDAC and 17 benign). The bile microbial beta diversity significantly differed between patients with PDAC vs. benign disease (Permanova p = 0.0173). The separation of PDAC from benign samples is clearly seen through unsupervised clustering of Aitchison distance. We found three genera to be of significantly lower abundance among PDAC samples vs. benign, adjusting for false discovery rate (FDR). These were Escherichia (FDR = 0.002) and two unclassified genera, one from Proteobacteria (FDR = 0.002) and one from Enterobacteriaceae (FDR = 0.011). In the same samples, the genus Streptococcus (FDR = 0.033) was found to be of increased abundance in the PDAC group. We show that patients with obstructive jaundice caused by PDAC have an altered microbiome composition in the bile compared to those with benign disease. These bile-based microbes could be developed into potential diagnostic and prognostic biomarkers for PDAC and warrant further investigation.
摘要：
胰腺导管腺癌（PDAC）的生存率非常差。肿瘤内微生物组可以影响胰腺肿瘤发生和化学耐药性，因此,患者生存。胆汁微生物群在PDAC中的作用尚不清楚。我们旨在定义胆汁微生物组特征，以有效区分良性和恶性胰胆管疾病引起的阻塞性黄疸患者的恶性肿瘤和良性肿瘤。从31例接受内镜逆行胰胆管造影（ERCP）或经皮肝穿刺胆管造影（PTC）的患者中获得了前瞻性胆汁样本。通过聚合酶链反应(PCR)扩增样品中存在的微生物的16SrRNA基因的可变区(V3-V4)并测序。该队列由12个PDAC组成，10胆总管结石,7例胆结石性胰腺炎和2例原发性硬化性胆管炎患者。使用16SrRNA方法，我们从29个个体(12个PDAC和17个良性)中鉴定出135个属.PDAC患者与PDAC患者之间的胆汁微生物β多样性显着不同。良性疾病（Permanovap=0.0173）。通过Aitchison距离的无监督聚类可以清楚地看到PDAC与良性样品的分离。我们发现PDAC样品中的三个属的丰度明显较低。良性,调整错误发现率(FDR)。这些是埃希氏菌（FDR=0.002）和两个未分类的属，一个来自变形杆菌（FDR=0.002），一个来自肠杆菌科（FDR=0.011）。在相同的样本中，在PDAC组中发现链球菌属（FDR=0.033）的丰度增加。我们表明，与良性疾病患者相比，由PDAC引起的阻塞性黄疸患者胆汁中的微生物组组成发生了改变。这些基于胆汁的微生物可以发展成为PDAC的潜在诊断和预后生物标志物，并值得进一步研究。
