1. Impairment of gut microbial biotin metabolism and host biotin status in severe obesity:effect of biotin and prebiotic supplementation on improved metabolism
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Belda, Eugeni, Voland, Lise, Tremaroli, Valentina, Falony, Gwen, Adriouch, Solia, Assmann, Karen E., Prifiti, Edi, Aron-Wisnewsky, Judith, Debedat, Jean, Le Roy, Tiphaine, Nielsen, Trine, Amouyal, Chloe, Andre, Sebastien, Andreelli, Fabrizio, Blueher, Matthias, Chakaroun, Rima, Chilloux, Julien, Coelho, Luis Pedro, Dao, Maria Carlota, Das, Promi, Fellahi, Soraya, Forslund, Sofia, Galleron, Nathalie, Hansen, Tue H., Holmes, Bridget, Ji, Boyang, Pedersen, Helle Krogh, Phuong Le, Le Chatelier, Emmanuelle, Lewinter, Christian, Manneras-Holm, Louise, Marquet, Florian, Myridakis, Antonis, Pelloux, Veronique, Pons, Nicolas, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe-Elie, Sokolovska, Nataliya, Søndertoft, Nadja B., Touch, Sothea, Vieira-Silva, Sara, Galan, Pilar, Holst, Jens, Gøtze, Jens Peter, Køber, Lars, Vestergaard, Henrik, Hansen, Torben, Hercberg, Serge, Oppert, Jean-Michel, Nielsen, Jens, Letunic, Ivica, Dumas, Marc-Emmanuel, Stumvoll, Michael, Pedersen, Oluf Borbye, Bork, Peer, Ehrlich, Stanislav Dusko, Zucker, Jean-Daniel, Baeckhed, Fredrik, Raes, Jeroen, Clement, Karine, Commission of the European Communities, Medical Research Council (MRC), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Inst Med, Dept Mol & Clin Med, Wallenberg Lab, University of Gothenburg (GU), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (COMUE) (USPC), MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Bordeaux (UB), Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Service de Diabétologie [CHU Pitié-Salpétrière], Laboratoire de chimie Macromoléculaire (CNRS UMR 5076), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universität Leipzig [Leipzig], Keck School of Medicine [Los Angeles], University of Southern California (USC), Nutrition et cerveau (U1213, U855), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Instituto de Medicina Molecular, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Imperial College London - National Heart and Lung Institute, and Division of Computational and Systems Medicine, Imperial College London, London, SW7 2AZ, UK
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EXPRESSION ,[SDV]Life Sciences [q-bio] ,Biotin ,Endocrinology and Diabetes ,Microbiology ,DIET ,Mice ,Humans ,Animals ,Obesity ,CHROMIUM PICOLINATE ,Inflammation ,Science & Technology ,OVERWEIGHT ,Gastroenterology & Hepatology ,Gastroenterology ,1103 Clinical Sciences ,Gastrointestinal Microbiome ,Obesity, Morbid ,MetaCardis Consortium ,Mice, Inbred C57BL ,nutrition ,Prebiotics ,Diabetes Mellitus, Type 2 ,Cardiovascular and Metabolic Diseases ,micronutrients ,Other Clinical Medicine ,diabetes mellitus ,Vitamin B Complex ,1114 Paediatrics and Reproductive Medicine ,intestinal bacteria ,HEALTH ,Life Sciences & Biomedicine - Abstract
ObjectivesGut 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.DesignWe 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.ResultsSevere 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.ConclusionStrategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity.Trial registration numberNCT02059538.
- Published
- 2022
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