Imperial College London
Alternate

ProfessorElaineHolmes

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor of Chemical Biology
 
 
 
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Contact

 

+44 (0)20 7594 3220elaine.holmes

 
 
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Location

 

661Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Hegade:2019:10.1111/liv.14069,
author = {Hegade, VS and Pechlivanis, A and McDonald, JA and Rees, D and Corrigan, M and Hirschfield, GM and Taylor-Robinson, SD and Holmes, E and Marchesi, JR and Kendrick, S and Jones, DE},
doi = {10.1111/liv.14069},
journal = {Liver International},
pages = {967--975},
title = {Autotaxin, bile acid profile and effect of IBAT inhibition in primary biliary cholangitis patients with pruritus},
url = {http://dx.doi.org/10.1111/liv.14069},
volume = {39},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND &AIMS: Pruritus is a common symptom in patients with primary biliary cholangitis (PBC) for which ileal bile acid transporter (IBAT) inhibition is emerging as a potential therapy. We explored the serum metabonome and gut microbiota profile in PBC patients with pruritus and investigated the effect of GSK2330672, an IBAT inhibitor. METHODS: We studied fasting serum bile acids (BAs), autotaxin and faecal microbiota in 22 PBC patients with pruritus at baseline and after two weeks of GSK2330672 treatment. Control group included 31 asymptomatic PBC patients and 18 healthy volunteers. BA profiling was done by ultraperformance liquid chromatography coupled to a mass spectrometry (UPLC-MS). Faecal microbiomes were analysed by 16S ribosomal RNA gene sequencing. RESULTS: In PBC patients with pruritus serum levels of total and glyco-conjugated primary BAs and autotaxin were significantly elevated. Autotaxin activity correlated significantly with tauro- and glyco-conjugated cholic acid (CA) and chenodeoxycholic acid (CDCA), both at baseline and after GSK2330672. GSK2330672 significantly reduced autotaxin and all tauro- and glyco- conjugated BAs and increased faecal levels of CA (p=0.048) and CDCA (p=0.027). Gut microbiota of PBC patients with pruritus was similar to control groups. GSK2330672 increased relative abundance of Firmicutes (p=0.033) and Clostridia (p=0.04) and decreased Bacteroidetes (p=0.033) and Bacteroidia (p=0.04). CONCLUSIONS: Pruritus in PBC does not show a distinct gut bacterial profile but is associated with elevated serum bile acid and autotaxin levels which decrease after IBAT inhibition. In cholestatic pruritus, a complex interplay between BAs and ATX is likely and may be modified by IBAT inhibition. This article is protected by copyright. All rights reserved.
AU  - Hegade,VS
AU  - Pechlivanis,A
AU  - McDonald,JA
AU  - Rees,D
AU  - Corrigan,M
AU  - Hirschfield,GM
AU  - Taylor-Robinson,SD
AU  - Holmes,E
AU  - Marchesi,JR
AU  - Kendrick,S
AU  - Jones,DE
DO  - 10.1111/liv.14069
EP  - 975
PY  - 2019///
SN  - 1478-3223
SP  - 967
TI  - Autotaxin, bile acid profile and effect of IBAT inhibition in primary biliary cholangitis patients with pruritus
T2  - Liver International
UR  - http://dx.doi.org/10.1111/liv.14069
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30735608
UR  - https://onlinelibrary.wiley.com/doi/full/10.1111/liv.14069
UR  - http://hdl.handle.net/10044/1/67152
VL  - 39
ER  -
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