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Autotaxin, bile acid profile and effect of ileal bile acid transporter inhibition in primary biliary cholangitis patients with pruritus.
- Source :
-
Liver international : official journal of the International Association for the Study of the Liver [Liver Int] 2019 May; Vol. 39 (5), pp. 967-975. Date of Electronic Publication: 2019 Feb 25. - Publication Year :
- 2019
-
Abstract
- 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.<br />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.<br />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).<br />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.<br /> (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Subjects :
- Adult
Aged
Biomarkers blood
Carrier Proteins
Case-Control Studies
Chenodeoxycholic Acid pharmacology
Cholic Acid pharmacology
Chromatography, Liquid
Feces chemistry
Feces microbiology
Female
Humans
Male
Membrane Glycoproteins
Middle Aged
Pruritus etiology
RNA, Ribosomal, 16S genetics
Tandem Mass Spectrometry
Bile Acids and Salts blood
Liver Cirrhosis, Biliary complications
Methylamines pharmacology
Phosphoric Diester Hydrolases blood
Pruritus blood
Pruritus drug therapy
Thiazepines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1478-3231
- Volume :
- 39
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Liver international : official journal of the International Association for the Study of the Liver
- Publication Type :
- Academic Journal
- Accession number :
- 30735608
- Full Text :
- https://doi.org/10.1111/liv.14069