Alterations in bile acid kinetics after bariatric surgery in patients with obesity with or without type 2 diabetesResearch in context
Annika Wahlström,
Ömrüm Aydin,
Lisa M. Olsson,
Wilhelm Sjöland,
Marcus Henricsson,
Annika Lundqvist,
Hanns-Ulrich Marschall,
Rutger Franken,
Arnold van de Laar,
Victor Gerdes,
Abraham S. Meijnikman,
Dag Hofsø,
Albert K. Groen,
Jøran Hjelmesæth,
Max Nieuwdorp,
Fredrik Bäckhed
Affiliations
Annika Wahlström
Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden
Ömrüm Aydin
Department of Internal and Vascular Medicine, Amsterdam UMC, Amsterdam, the Netherlands; Department of Internal Medicine, Spaarne Gasthuis, Hoofddorp, the Netherlands
Lisa M. Olsson
Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden
Wilhelm Sjöland
Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden
Marcus Henricsson
Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden
Annika Lundqvist
Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden
Hanns-Ulrich Marschall
Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden
Rutger Franken
Department of Surgery, Spaarne Hospital, Hoofddorp, the Netherlands
Arnold van de Laar
Department of Surgery, Spaarne Hospital, Hoofddorp, the Netherlands
Victor Gerdes
Department of Internal and Vascular Medicine, Amsterdam UMC, Amsterdam, the Netherlands
Abraham S. Meijnikman
Department of Internal and Vascular Medicine, Amsterdam UMC, Amsterdam, the Netherlands
Dag Hofsø
Department of Endocrinology, Obesity and Nutrition, Vestfold Hospital Trust, Tønsberg, Norway
Albert K. Groen
Experimental Vascular Medicine, Amsterdam UMC, Amsterdam, the Netherlands
Jøran Hjelmesæth
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
Max Nieuwdorp
Department of Internal and Vascular Medicine, Amsterdam UMC, Amsterdam, the Netherlands; Experimental Vascular Medicine, Amsterdam UMC, Amsterdam, the Netherlands
Fredrik Bäckhed
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; Corresponding author. Department of Molecular and Clinical Medicine, Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Gothenburg S-413 45, Sweden.
Summary: 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.
