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

Lookup NU author(s): Dr Jess Dyson, Professor David Jones

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. 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.

Publication metadata

Author(s): Martinez-Gili L, Pechlivanis A, McDonald JAK, Begum S, Badrock J, Dyson JK, Jones R, Hirschfield G, Ryder SD, Sandford R, Rushbrook S, Thorburn D, Taylor-Robinson SD, Crossey MME, Marchesi JR, Mells G, Holmes E, Jones D

Publication type: Article

Publication status: Published

Journal: Gut Microbes

Year: 2023

Volume: 15

Issue: 1

Online publication date: 16/05/2023

Acceptance date: 21/04/2023

Date deposited: 31/05/2023

ISSN (print): 1949-0976

ISSN (electronic): 1949-0984

Publisher: Taylor and Francis Ltd

URL: https://doi.org/10.1080/19490976.2023.2208501

DOI: 10.1080/19490976.2023.2208501

Data Access 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

PubMed id: 37191344

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