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

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Title: Autotaxin, bile acid profile and effect of IBAT inhibition in primary biliary cholangitis patients with pruritus
Authors: Hegade, VS
Pechlivanis, A
McDonald, JA
Rees, D
Corrigan, M
Hirschfield, GM
Taylor-Robinson, SD
Holmes, E
Marchesi, JR
Kendrick, S
Jones, DE
Item Type: Journal Article
Abstract: 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.
Issue Date: May-2019
Date of Acceptance: 23-Jan-2019
URI: http://hdl.handle.net/10044/1/67152
DOI: https://doi.org/10.1111/liv.14069
ISSN: 1478-3223
Publisher: Wiley
Start Page: 967
End Page: 975
Journal / Book Title: Liver International
Volume: 39
Issue: 5
Copyright Statement: © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. This is the pre-peer reviewed version of the following article: Hegade, VS, Pechlivanis, A, McDonald, JAK, et al. Autotaxin, bile acid profile and effect of ileal bile acid transporter inhibition in primary biliary cholangitis patients with pruritus. Liver Int. 2019; 39: 967– 975, which has been published in final form at https://doi.org/10.1111/liv.14069
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: BH124127
Keywords: Science & Technology
Life Sciences & Biomedicine
Gastroenterology & Hepatology
metabonome
microbiota
PBC
pruritus
QUALITY-OF-LIFE
DOUBLE-BLIND
INTESTINAL MICROBIOTA
CHOLESTATIC LIVER
SERUM
CIRRHOSIS
METABOLISM
BIOMARKERS
BINDING
INJURY
PBC
metabonome
microbiota
pruritus
PBC
metabonome
microbiota
pruritus
Gastroenterology & Hepatology
1103 Clinical Sciences
Publication Status: Published
Conference Place: United States
Online Publication Date: 2019-02-08
Appears in Collections:Department of Metabolism, Digestion and Reproduction