Bacterial and metabolic phenotypes associated with inadequate response to ursodeoxycholic acid treatment in primary biliary cholangitis

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Martinez-Gili, Laura, Pechlivanis, Alexandros, McDonald, Julie A.K., Begum, Sofina, Badrock, Jonathan, Dyson, Jessica K., Jones, Rebecca, Hirschfield, Gideon, Ryder, Stephen D., Sandford, Richard, Rushbrook, Simon, Thorburn, Douglas, Taylor-Robinson, Simon D., Crossey, Mary M.E., Marchesi, Julian R., Mells, George, Holmes, Elaine and Jones, David (2023) Bacterial and metabolic phenotypes associated with inadequate response to ursodeoxycholic acid treatment in primary biliary cholangitis. Gut Microbes, 15 (1). ISSN 1949-0976

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Abstract

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease with ursodeoxycholic acid (UDCA) as first-line treatment. Poor response to UDCA is associated with a higher risk of progressing to cirrhosis, but the underlying mechanisms are unclear. UDCA modulates the composition of primary and bacterial-derived bile acids (BAs). We characterized the phenotypic response to UDCA based on BA and bacterial profiles of PBC patients treated with UDCA. Patients from the UK-PBC cohort (n = 419) treated with UDCA for a minimum of 12-months were assessed using the Barcelona dynamic response criteria. BAs from serum, urine, and feces were analyzed using Ultra-High-Performance Liquid Chromatography-Mass Spectrometry and fecal bacterial composition measured using 16S rRNA gene sequencing. We identified 191 non-responders, 212 responders, and a subgroup of responders with persistently elevated liver biomarkers (n = 16). Responders had higher fecal secondary and tertiary BAs than non-responders and lower urinary bile acid abundances, with the exception of 12-dehydrocholic acid, which was higher in responders. The sub-group of responders with poor liver function showed lower alpha-diversity evenness, lower abundance of fecal secondary and tertiary BAs than the other groups and lower levels of phyla with BA-deconjugation capacity (Actinobacteriota/Actinomycetota, Desulfobacterota, Verrucomicrobiota) compared to responders. UDCA dynamic response was associated with an increased capacity to generate oxo-/epimerized secondary BAs. 12-dehydrocholic acid is a potential biomarker of treatment response. Lower alpha-diversity and lower abundance of bacteria with BA deconjugation capacity might be associated with an incomplete response to treatment in some patients.

Item Type: Article
Additional Information: Data availability statement: 16S rRNA gene amplicon sequences have been deposited in the European Nucleotide Archive database with reference PRJEB44791. Data sharing will be considered upon reasonable request. https://www.ebi.ac.uk/ena/browser/view/PRJEB44791
Uncontrolled Keywords: bile acids,gut-liver-kidney axis,microbiota,pbc,udca,microbiology,gastroenterology,microbiology (medical),infectious diseases,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2400/2404
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 14 Jul 2026 08:01
Last Modified: 14 Jul 2026 17:55
URI: https://ueaeprints.uea.ac.uk/id/eprint/103834
DOI: 10.1080/19490976.2023.2208501

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