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Autotaxin, bile acid profile and effect of ileal bile acid transporter inhibition in primary biliary cholangitis patients with pruritus

Lookup NU author(s): Dr Vinod Hegade, Dr Stuart Kendrick, Professor David Jones

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Abstract

© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Background and 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 2 weeks of GSK2330672 treatment. Control group included 31 asymptomatic PBC patients and 18 healthy volunteers. BA profiling was done by ultra performance 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 the 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 autotaxin is likely and may be modified by IBAT inhibition.

Publication metadata

Author(s): Hegade VS, Pechlivanis A, McDonald JAK, Rees D, Corrigan M, Hirschfield GM, Taylor-Robinson SD, Holmes E, Marchesi JR, Kendrick S, Jones DE

Publication type: Article

Publication status: Published

Journal: Liver International

Year: 2019

Volume: 39

Issue: 5

Pages: 967-975

Print publication date: 01/05/2019

Online publication date: 08/02/2019

Acceptance date: 23/01/2019

ISSN (print): 1478-3223

ISSN (electronic): 1478-3231

Publisher: Wiley-Blackwell Publishing Ltd.

URL: https://doi.org/10.1111/liv.14069

DOI: 10.1111/liv.14069

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