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

Laura Martinez-Gili; Alexandros Pechlivanis; Julie A K McDonald; Sofina Begum; Jonathan Badrock; Jessica K Dyson; Rebecca Jones; Gideon Hirschfield; Stephen D Ryder; Richard Sandford; Simon Rushbrook; Douglas Thorburn; Simon D Taylor-Robinson; Mary M E Crossey; Julian R Marchesi; George Mells; Elaine Holmes; David Jones

doi:10.1080/19490976.2023.2208501

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

Journal article

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

Laura Martinez-Gili, Alexandros Pechlivanis, Julie A K McDonald, Sofina Begum, Jonathan Badrock, Jessica K Dyson, Rebecca Jones, Gideon Hirschfield, Stephen D Ryder, Richard Sandford, …

Gut microbes, Vol.15(1), 2208501

2023

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

PMID: 37191344

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Abstract

Bacteria - genetics

Bile Acids and Salts - therapeutic use

Biomarkers

Cholagogues and Choleretics - therapeutic use

Dehydrocholic Acid - therapeutic use

Gastrointestinal Microbiome

Humans

Liver Cirrhosis, Biliary - drug therapy

Phenotype

RNA, Ribosomal, 16S - genetics

Ursodeoxycholic Acid - therapeutic use

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.

Details

Title: Bacterial and metabolic phenotypes associated with inadequate response to ursodeoxycholic acid treatment in primary biliary cholangitis
Authors/Creators: Laura Martinez-Gili - Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
Alexandros Pechlivanis - Biomic_Auth, Bioanalysis and Omics Laboratory, Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Balkan Centre, Thessaloniki, Greece
Julie A K McDonald - Imperial College London
Sofina Begum - Imperial College London
Jonathan Badrock - University of Cambridge
Jessica K Dyson - Newcastle upon Tyne Hospitals NHS Foundation Trust
Rebecca Jones - St James's University Hospital
Gideon Hirschfield - NIHR Birmingham Biomedical Research Centre
Stephen D Ryder - Nottingham University Hospitals NHS Trust
Richard Sandford - University of Cambridge
Simon Rushbrook - Norfolk and Norwich University Hospital
Douglas Thorburn - The Royal Free Hospital
Simon D Taylor-Robinson - Imperial College London
Mary M E Crossey - Imperial College London
Julian R Marchesi - Imperial College London
George Mells - University of Cambridge
Elaine Holmes - Murdoch University, Centre for Computational and Systems Medicine
David Jones - Institute of Translational and Clinical Research, Newcastle University, Newcastle upon Tyne, UK
Publication Details: Gut microbes, Vol.15(1), 2208501
Publisher: Published with license by Taylor & Francis Group, LLC.
Grant note: MR/L001489/1 / Medical Research Council Department of Health
Identifiers: 991005581069107891
Murdoch Affiliation: Centre for Computational and Systems Medicine
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.120 Inflammatory Bowel Diseases & Infections; 1.120.384 Gut Microbiota
Web Of Science research areas: Gastroenterology & Hepatology; Microbiology
ESI research areas: Microbiology