Dysbiosis and Altered Bile Acids: Are They Clues to Cyclic Exacerbation of Injury in PSC?

Bret T. Petersen, MD, FASGE reviewing Liwinski T, et al. Gut 2019 June 26.

Perturbations of the colonic microbiome are seen in a variety of gastrointestinal diseases, including primary sclerosing cholangitis (PSC). In this study, the investigators compared the oral, duodenal, and biliary microbiome (by genetic sequencing of microbial RNA encoding genes) and the biliary bile acid composition (by mass spectrometry) in 43 patients with PSC and 22 control patients with choledocholithiasis or papillary adenoma alone, while excluding those presenting with bacterial cholangitis, recent endoscopic retrograde cholangiography, or recent antibiotic administration. 

In all patients, the biliary microbiome was distinct from the other regions of the upper intestinal tract, and the microbiome in all areas was distinctly different between those with PSC and those without. Compared to controls, the bile of PSC patients exhibited significantly lower biodiversity (p=0.013) and greater populations of Enterococcus faecalis, which correlated with the concentration of noxious biliary taurolithocholic acid (r=0.60, p=0.0021). Hence, the authors demonstrated both altered microbiomes and concurrent increases in a secondary bile acid with proinflammatory and carcinogenic properties.


Comment:
In contrast to our presumptions about sterility of the native biliary tree, these authors and others have demonstrated microbial life to be common in both normal bile ducts and those with various pathologies. The biliary dysbiosis identified here in patients with PSC was greater and more uniform than seen in older studies, perhaps as a result of the highly sophisticated methods employed. The finding of more injurious bacterial populations and bile acid distributions prompts further hypotheses about cause and effect and potential interventions to reduce progressive disease.

Bret T. Petersen, MD, FASGE
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Citation(s):
Liwinski T, Zenouzi R, John C, et al. Alterations of the bile microbiome in primary sclerosing cholangitis. Gut 2019 June 26. (Epub ahead of print) (https://doi.org/10.1136/gutjnl-2019-318416)