1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Gut. 2020 Apr;69(4):665-672. doi: 10.1136/gutjnl-2019-318416. Epub 2019 Jun 26.
Patients with primary sclerosing cholangitis (PSC) display an altered colonic microbiome compared with healthy controls. However, little is known on the bile duct microbiome and its interplay with bile acid metabolism in PSC.
Patients with PSC (n=43) and controls without sclerosing cholangitis (n=22) requiring endoscopic retrograde cholangiography were included prospectively. Leading indications in controls were sporadic choledocholithiasis and papillary adenoma. A total of 260 biospecimens were collected from the oral cavity, duodenal fluid and mucosa and ductal bile. Microbiomes of the upper alimentary tract and ductal bile were profiled by sequencing the 16S-rRNA-encoding gene (V1-V2). Bile fluid bile acid composition was measured by high-performance liquid chromatography mass spectrometry and validated in an external cohort (n=20).
The bile fluid harboured a diverse microbiome that was distinct from the oral cavity, the duodenal fluid and duodenal mucosa communities. The upper alimentary tract microbiome differed between PSC patients and controls. However, the strongest differences between PSC patients and controls were observed in the ductal bile fluid, including reduced biodiversity (Shannon entropy, p=0.0127) and increase of pathogen (FDR=4.18×10) in PSC. abundance in ductal bile was strongly correlated with concentration of the noxious secondary bile acid taurolithocholic acid (r=0.60, p=0.0021).
PSC is characterised by an altered microbiome of the upper alimentary tract and bile ducts. Biliary dysbiosis is linked with increased concentrations of the proinflammatory and potentially cancerogenic agent taurolithocholic acid.
原发性硬化性胆管炎（PSC）患者的结肠微生物组与健康对照组相比发生了改变。然而，关于胆管微生物组及其与 PSC 中胆汁酸代谢的相互作用知之甚少。
前瞻性纳入需要内镜逆行胰胆管造影术的 PSC 患者（n=43）和无硬化性胆管炎的对照组（n=22）。对照组的主要适应证为散发性胆总管结石和乳头腺瘤。共从口腔、十二指肠液和黏膜以及胆管胆汁中采集了 260 个生物样本。通过测序 16S-rRNA 编码基因（V1-V2）对上消化道和胆管胆汁的微生物组进行了分析。通过高效液相色谱-质谱法测量胆汁液胆汁酸组成，并在外部队列（n=20）中进行了验证。
胆管胆汁中存在丰富的微生物群，与口腔、十二指肠液和十二指肠黏膜群落明显不同。上消化道微生物群在 PSC 患者和对照组之间存在差异。然而，在胆管胆汁中观察到 PSC 患者和对照组之间最强的差异，包括生物多样性降低（Shannon 熵，p=0.0127）和病原体增加（FDR=4.18×10）。胆管胆汁中的丰度与有害次级胆汁酸牛磺胆酸的浓度呈强烈相关（r=0.60，p=0.0021）。
PSC 的特征是上消化道和胆管微生物组发生改变。胆道菌群失调与促炎和潜在致癌剂牛磺胆酸浓度增加有关。
