A microbiological assessment of the human biliary tract in health and disease

Warburton, Richard (2017) A microbiological assessment of the human biliary tract in health and disease. Doctoral thesis, University of East Anglia.

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Abstract

The gastrointestinal tract in humans is home to 100 trillion bacteria, collectively referred to as the gut microbiota. This ‘bacterial organ’ has a vital role to play in both health and disease. Conventional wisdom dictates that bile in normal biliary systems is sterile. However, the liver is continually exposed to gut bacteria and their metabolites via the portal vein. Recent studies have identified bacterial populations within the biliary system of symptomatic patients undergoing cholecystectomy or biliary intervention. In this study we identified that there is a complex biliary microbiota within a normal biliary tract.

Many bacterial species were isolated from the bile of patients undergoing hepatic resection or cholecystectomy and their identity established through sequencing their 16S ribosomal RNA gene. These included Staphylococcus, Micrococcus,
Enterococcus and Bacillus sp. Isolated bacteria were examined for their resistance to bile salts and the results suggested that all the isolates were able to survive under physiologically relevant bile concentrations with some isolates expressing bile salt hydrolase activity. An in-depth analysis of the biliary microbiome using 16S-based metataxonomics was performed. Results suggested that human bile has a diverse and varied microbiota, a large proportion of which were unculturable. 34 different genera were identified with Pseudomonas being the most prevalent. Dysbiosis was noted between diseased (e.g. gallstone and biliary obstruction) and normal samples.

The gut microbiota of the two most common chronic biliary conditions, Primary Sclerosing Cholangits and Primary Biliary Cholangitis, were also examined to see if dysbiosis was present. There is an emerging dysbiosis in patients with chronic cholestatic liver disease, although these results were possibly restricted through patient treatment with ursodeoxycholic acid.

This study is the first to describe a complex biliary microbiota in normal human bile and in the future a detailed understanding of the function of this microbiota may provide a therapeutic target for biliary disease.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User:	Jackie Webb
Date Deposited:	21 May 2018 08:40
Last Modified:	31 May 2018 00:38
URI:	https://ueaeprints.uea.ac.uk/id/eprint/67133
DOI:

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