Bile acid–farnesoid X receptor–fibroblast growth factor 19 axis in patients with short bowel syndrome: The randomized, glepaglutide phase 2 trial

• DOI: 10.1002/jpen.2224
• Publication Date: 2021-07-21T05:50:45Z
• Authors: Mark Krogh Hviste...; Rahim Mohammad Naimi; Svend Høime Hansen; Jens Frederik Reh...; Hannelouise Kissow; Jens Pedersen; Lars Ove Dragsted; David Peick Sonne; Filip Krag Knop; Palle Bekker Jepp...
• Keywords: FGF19; Farnesoid X receptor; Enterohepatic circulation; Short Bowel Syndrome

The gut-liver axis and enterohepatic circulation have gained increasing attention lately. Patients with short bowel syndrome (SBS) are, in fact, human knock-out models that may assist the understanding of bile acid synthesis regulation. We evaluated effect glepaglutide (a long-acting glucagon-like peptide-2 analog) on (the acids liver biochemistry patients SBS).In a single-center, double-blinded, dose-finding, crossover phase 2 trial, 18 SBS were randomly assigned to 3 treatment arms (0.1, 1, 10 mg) daily subcutaneous injections for weeks. washout period between periods was 4-8 Measurements performed at baseline end each included postprandial plasma samples fibroblast growth factor 19 (FGF19), 7α-hydroxy-4-cholesten-3-one (C4), total excretion fecal acids, gene expression farnesoid X receptor (FXR) intestinal mucosal biopsies, biochemistry.Compared baseline, median (interquartile range) response (area under curve 0-2h) FGF19 increased by 150 h × ng/L (41, 195; P = 0.001) C4 decreased 82 µg/L (-169, -28; p 0.010) 10-mg dose. FXR did not change any groups. Alkaline phosphatase significantly decreased.Glepaglutide stimulate acid/FXR/FGF19 axis, leading concentrations FGF19. Thereby, ameliorate accelerated de novo play role prevention and/or failure-associated disease.