RT Journal Article
SR Electronic
T1 Alterations of the bile microbiome in primary sclerosing cholangitis
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP gutjnl-2019-318416
DO 10.1136/gutjnl-2019-318416
A1 Timur Liwinski
A1 Roman Zenouzi
A1 Clara John
A1 Hanno Ehlken
A1 Malte C Rühlemann
A1 Corinna Bang
A1 Stefan Groth
A1 Wolfgang Lieb
A1 Marcus Kantowski
A1 Nils Andersen
A1 Guido Schachschal
A1 Tom H Karlsen
A1 Johannes R Hov
A1 Thomas Rösch
A1 Ansgar W Lohse
A1 Joerg Heeren
A1 Andre Franke
A1 Christoph Schramm
YR 2019
UL http://gut.bmj.com/content/early/2019/06/26/gutjnl-2019-318416.abstract
AB Background 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.Methods 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).Results 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 Enterococcus faecalis (FDR=4.18×10−5) in PSC. Enterococcus abundance in ductal bile was strongly correlated with concentration of the noxious secondary bile acid taurolithocholic acid (r=0.60, p=0.0021).Conclusion 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.