Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism.

Autor: Belda E; Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France.; Integrative Phenomics, Paris, France., Voland L; Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France., Tremaroli V; Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, Goteborg, Sweden., Falony G; Center for Microbiology, VIB, Leuven, Belgium.; Vlaams Instituut voor Biotechnologie, VIB-KU Leuven, Heverlee, Flanders, Belgium., Adriouch S; Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France., Assmann KE; Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France., Prifti E; Unité de Modélisation Mathématique et Informatique des Systèmes Complexes, UMMISCO, Sorbonne Université, IRD, Bondy, France., Aron-Wisnewsky J; Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France.; Department of Nutrition, Pitié-Salpêtrière Hospital, Assistance Publique - Hopitaux de Paris, Paris, France., Debédat J; Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France., Le Roy T; Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France., Nielsen T; Center for Basic Metabolic Research, Novo Nordisk Foundation, University of Copenhagen, Kobenhavn, Denmark., Amouyal C; Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France., André S; Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France., Andreelli F; Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France., Blüher M; Medical Department III - Endocrinology, Nephrology, Rheumatology - Medical Center, Faculty of Medicine, University of Leipzig, Leipzig, Germany., Chakaroun R; Medical Department III - Endocrinology, Nephrology, Rheumatology - Medical Center, Faculty of Medicine, University of Leipzig, Leipzig, Germany., Chilloux J; Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London Faculty of Medicine, London, UK., Coelho LP; Structural and Computational Biology, European Molecular Biology Laboratory, Heidelberg, Germany.; Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Dao MC; Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France., Das P; Department of Biology, Chalmers University of Technology, Goteborg, Sweden., Fellahi S; Functional Unit, Biochemistry and Hormonology Department, enon Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.; Saint-Antoine Research Center, Sorbonne Université, INSERM, Paris, France., Forslund S; Max Delbrück Center for Molecular Medicine, MDC, Berlin-Buch, Germany., Galleron N; MetaGenoPolis, Université Paris-Saclay, INRAE, Jouy-en-Josas, France., Hansen TH; Center for Basic Metabolic Research, Novo Nordisk Foundation, University of Copenhagen, Kobenhavn, Denmark., Holmes B; Centre Daniel Carasso, Global Nutrition Department, Danone Nutricia Research, Palaiseau, France., Ji B; Department of Biology, Chalmers University of Technology, Goteborg, Sweden., Krogh Pedersen H; Center for Basic Metabolic Research, Novo Nordisk Foundation, University of Copenhagen, Kobenhavn, Denmark., Le P; Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France., Le Chatelier E; MetaGenoPolis, Université Paris-Saclay, INRAE, Jouy-en-Josas, France., Lewinter C; Department of Cardiology, Rigshospitalet, Kobenhavn, Denmark., Mannerås-Holm L; Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, Goteborg, Sweden., Marquet F; Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France., Myridakis A; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK., Pelloux V; Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France., Pons N; MetaGenoPolis, Université Paris-Saclay, INRAE, Jouy-en-Josas, France., Quinquis B; MetaGenoPolis, Université Paris-Saclay, INRAE, Jouy-en-Josas, France., Rouault C; Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France., Roume H; MetaGenoPolis, Université Paris-Saclay, INRAE, Jouy-en-Josas, France., Salem JE; Department of Pharmacology and CIC-1421, Assistance Publique-Hôpitaux de Paris, AP-HP, Pitié-Salpêtrière Hospital, Paris, France., Sokolovska N; Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France., Søndertoft NB; Center for Basic Metabolic Research, Novo Nordisk Foundation, University of Copenhagen, Kobenhavn, Denmark., Touch S; Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France., Vieira-Silva S; Center for Microbiology, VIB, Leuven, Belgium.; Vlaams Instituut voor Biotechnologie, VIB-KU Leuven, Heverlee, Flanders, Belgium., Galan P; Nutritional Epidemiology Unit, INSERM, INRAE, CNAM, Paris 13 University, Bobigny, France., Holst J; Center for Basic Metabolic Research, Novo Nordisk Foundation, University of Copenhagen, Kobenhavn, Denmark., Gøtze JP; Department of Clinical Biochemistry, Rigshospitalet, Kobenhavn, Denmark., Køber L; Department of Cardiology, Rigshospitalet, Kobenhavn, Denmark., Vestergaard H; Center for Basic Metabolic Research, Novo Nordisk Foundation, University of Copenhagen, Kobenhavn, Denmark.; Steno Diabetes Center, Copenhagen, Gentofte, Denmark., Hansen T; Center for Basic Metabolic Research, Novo Nordisk Foundation, University of Copenhagen, Kobenhavn, Denmark.; Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark., Hercberg S; Nutritional Epidemiology Unit, INSERM, INRAE, CNAM, Paris 13 University, Bobigny, France., Oppert JM; Department of Nutrition, Pitié-Salpêtrière Hospital, Assistance Publique - Hopitaux de Paris, Paris, France., Nielsen J; Department of Biology, Chalmers University of Technology, Goteborg, Sweden., Letunic I; Biobyte Solution, GmbH, Heidelberg, Germany., Dumas ME; Department of Surgery and Cancer, Section of Computational and Systems Medicine, Imperial College London, London, UK.; National Heart & Lung Institute, Section of Genomic & Environmental Medicine, Imperial College London, London, UK., Stumvoll M; Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München, University of Leipzig Faculty of Medicine, Leipzig, Germany., Pedersen OB; Center for Basic Metabolic Research, Novo Nordisk Foundation, University of Copenhagen, Kobenhavn, Denmark., Bork P; Structural and Computational Biology, European Molecular Biology Laboratory, Heidelberg, Germany.; Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Ehrlich SD; MetaGenoPolis, Université Paris-Saclay, INRAE, Jouy-en-Josas, France.; Center for Host Microbiome Interactions, King's College London Dental Institute, London, UK., Zucker JD; Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France.; Unité de Modélisation Mathématique et Informatique des Systèmes Complexes, UMMISCO, Sorbonne Université, IRD, Bondy, France., Bäckhed F; Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, Goteborg, Sweden., Raes J; Center for Microbiology, VIB, Leuven, Belgium.; Vlaams Instituut voor Biotechnologie, VIB-KU Leuven, Heverlee, Flanders, Belgium., Clément K; Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France karine.clement2@gmail.com.; Department of Nutrition, Pitié-Salpêtrière Hospital, Assistance Publique - Hopitaux de Paris, Paris, France.
Jazyk: angličtina
Zdroj: Gut [Gut] 2022 Dec; Vol. 71 (12), pp. 2463-2480. Date of Electronic Publication: 2022 Jan 11.
DOI: 10.1136/gutjnl-2021-325753
Abstrakt: Objectives: Gut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome's functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation.
Design: We performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice.
Results: Severe obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration.
Conclusion: Strategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity.
Trial Registration Number: NCT02059538.
Competing Interests: Competing interests: KC is a consultant for Danone Research, Ysopia and CONFO therapeutics for work not associated with this study. KC held a collaborative research contract with Danone Research in the context of MetaCardis project. FB is a shareholder of Implexion pharma AB. MB received lecture and/or consultancy fees from AstraZeneca, Boehringer-Ingelheim, Lilly, Novo Nordisk, Novartis and Sanofi.
(© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze: MEDLINE