Alterations in bile acid kinetics after bariatric surgery in patients with obesity with or without type 2 diabetes.

Autor:	Wahlström A; Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden., Aydin Ö; Department of Internal and Vascular Medicine, Amsterdam UMC, Amsterdam, the Netherlands; Department of Internal Medicine, Spaarne Gasthuis, Hoofddorp, the Netherlands., Olsson LM; Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden., Sjöland W; Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden., Henricsson M; Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden., Lundqvist A; Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden., Marschall HU; Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden., Franken R; Department of Surgery, Spaarne Hospital, Hoofddorp, the Netherlands., van de Laar A; Department of Surgery, Spaarne Hospital, Hoofddorp, the Netherlands., Gerdes V; Department of Internal and Vascular Medicine, Amsterdam UMC, Amsterdam, the Netherlands., Meijnikman AS; Department of Internal and Vascular Medicine, Amsterdam UMC, Amsterdam, the Netherlands., Hofsø D; Department of Endocrinology, Obesity and Nutrition, Vestfold Hospital Trust, Tønsberg, Norway., Groen AK; Experimental Vascular Medicine, Amsterdam UMC, Amsterdam, the Netherlands., Hjelmesæth J; Department of Endocrinology, Obesity and Nutrition, Vestfold Hospital Trust, Tønsberg, Norway; Department of Endocrinology, Morbid Obesity and Preventive Medicine, Institute of Clinical Medicine, University of Oslo, Norway., Nieuwdorp M; Department of Internal and Vascular Medicine, Amsterdam UMC, Amsterdam, the Netherlands; Experimental Vascular Medicine, Amsterdam UMC, Amsterdam, the Netherlands., Bäckhed F; Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark; Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Physiology, Gothenburg, Sweden. Electronic address: Fredrik.Backhed@wlab.gu.se.
Jazyk:	angličtina
Zdroj:	EBioMedicine [EBioMedicine] 2024 Aug; Vol. 106, pp. 105265. Date of Electronic Publication: 2024 Aug 02.
DOI:	10.1016/j.ebiom.2024.105265
Abstrakt:	Background: Bariatric surgery is an effective treatment option for obesity and provides long-term weight loss and positive effects on metabolism, but the underlying mechanisms are poorly understood. Alterations in bile acid metabolism have been suggested as a potential contributing factor, but comprehensive studies in humans are lacking. Methods: In this study, we analysed the postprandial responses of bile acids, C4 and FGF19 in plasma, and excretion of bile acids in faeces, before and after bariatric surgery in patients (n = 38; 74% females) with obesity with or without type 2 diabetes from the BARIA cohort. Findings: We observed that total fasting plasma bile acid levels increased, and faecal excretion of bile acids decreased after surgery suggesting increased reabsorption of bile acids. Consistent with increased bile acid levels after surgery we observed increased postprandial levels of FGF19 and suppression of the bile acid synthesis marker C4, suggesting increased FXR activation in the gut. We also noted that a subset of bile acids had altered postprandial responses before and after surgery. Finally, fasting plasma levels of 6α-hydroxylated bile acids, which are TGR5 agonists and associated with improved glucose metabolism, were increased after surgery and one of them, HDCA, covaried with diabetes remission in an independent cohort. Interpretation: Our findings provide new insights regarding bile acid kinetics and suggest that bariatric surgery in humans alters bile acid profiles leading to activation of FXR and TGR5, which may contribute to weight loss, improvements in glucose metabolism, and diabetes remission. Funding: Novo Nordisk Fonden, Leducq Foundation, Swedish Heart-Lung Foundation, Knut and Alice Wallenberg Foundation, the ALF-agreement, ZonMw. Competing Interests: Declaration of interests F.B. receives research funding from Biogaia AB, is co-founder and shareholder of Roxbiosens Inc and Implexion AB, and is on the scientific advisory board of Bactolife A/S. L.O is co-founder and shareholder of Roxbiosens Inc. V.G. receives research funding from Spaarne Gastuis. M.N is member of the Scientific Advisory Board of and holds equity in Caelus Pharmaceuticals and receives research funding from and holds equity in Ami therapeutics, the Netherlands. However, none of these possible conflicts of interest bear direct relations to the content of the current paper. (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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