Pedersen, Helle Krogh, Gudmundsdottir, Valborg, Nielsen, Henrik Bjørn, Hyotylainen, Tuulia, Nielsen, Trine, Jensen, Benjamin A H, Forslund, Kristoffer, Hildebrand, Falk, Prifti, Edi, Falony, Gwen, Le Chatelier, Emmanuelle, Levenez, Florence, Dore, Joel, Mattila, Ismo, Plichta, Damian R, Pöhö, Päivi, Hellgren, Lars I, Arumugam, Manimozhiyan, Sunagawa, Shinichi, Vieira-Silva, Sara, Jørgensen, Torben, Holm, Jacob Bak, Trošt, Kajetan, Kristiansen, Karsten, Brix, Susanne, Raes, Jeroen, Wang, Jun, Hansen, Torben, Bork, Peer, Brunak, Søren, Oresic, Matej, Ehrlich, S. Dusko, Pedersen, Oluf, MetaHIT Consortium, ., Almeida, Mathieu, Batto, Jean-Michel, Blottiere, Hervé, Cultrone, Antonietta, Delorme, Christine, Dervyn, Rozenn, Guedon, Eric, Haimet, Florence, Jamet, Alexandre, Juste, Catherine, Kennedy, Sean, Kaci, Ghalia, Kleerebezem, Michiel, Layec, Séverine, Leclerc, Marion, Léonard, Pierre, Maguin, Emmanuelle, Manichanh, Chaysavanh, Pons, Nicolas, Renault, Pierre, Sanchez, Nicolas, Van De Guchte, Maarten, Van Hylckama Vlieg, Johan, Vandemeulebrouck, Gaetana, Winogradsky, Yohanan, Center for Biological Sequence Analysis - Department of Systems Biology, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), University of Denmark, Turku Centre for Biotechnology, University of Turku-Åbo Academy University, Åbo Akademi University [Turku], Örebro University, VTT Technical Research Centre of Finland (VTT), 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), Laboratory of Genomics and Molecular Biomedicine - Department of Biology, University of Copenhagen = Københavns Universitet (UCPH), European Molecular Biology Laboratory, Department of Bioscience Engineering, University of Antwerp (UA), Center for the Biology of Disease, VIB, MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (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), Centter for the Biology of Disease, Department of Microbiology and Immunology, Rega Institute for Medical Research, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Steno Diabetes Center, Faculty of Pharmacy, University of Valencia, Institute of Microbiology, Université de Lausanne = University of Lausanne (UNIL), Centre for the Biology of Disease, Research Centre for Prevention and Health - Centre for Health, Glostrup Hospital, Beijing Genomics Institute [Shenzhen] (BGI), Vrije Universiteit Brussel [Bruxelles] (VUB), Princess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Macau University of Science and Technology (MUST), Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Faculty of Health Sciences, Aarhus University [Aarhus], Molecular Medicine Partnership Unit, Heidelberg University, Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Department of Bioinformatics, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Disease Systems Biology [Copenhagen], Novo Nordisk Foundation Center for Protein Research (CPR), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Health and Medical Sciences, Centre for Biotechnology, Silesian University of Technology, Université Paris-Saclay, Centre for Host–Microbiome Interactions - Dental Institute Central Office, King‘s College London, Guys Hospital, Génie et Microbiologie des Procédés Alimentaires (GMPA), Département Microbiologie et Chaîne Alimentaire (MICA), Danone Research, Groupe Danone, International Human Microbiome Standards [FP7-HEALTH-2010-261376], Metagenopolis [ANR-11-DPBS-0001], Novo Nordisk Foundation, Lundbeck Foundation, European Project: 222720,EC | FP7 | SP1 | KBBE ,FP7-KBBE-2007-2A,TORNADO(2009), Technical University of Denmark [Lyngby] (DTU), University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), University of Copenhagen = Københavns Universitet (KU), Jouy-en-Josas, 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) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], Université de Lausanne (UNIL), BGI Shenzhen, Vrije University, University of Heidelberg, Max Delbrück Center for Molecular Medicine, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Health and Medical Sciences, US 1367 MGP MetaGénoPolis, Laboratory of Microbiology, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Digestive System Research Unit, Vall d'Hebron University Hospital [Barcelona], European Project: 201052, Faculty of Sciences and Bioengineering Sciences, Microbial Interactions, Department of Bio-engineering Sciences, and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
MetaHIT Consortium: Almeida M, Antolin M, Artiguenave F, Batto JM, Bertalan M, Blottiere H, Boruel N, Brechot C, Bruls T, Burgdorf K, Casellas F, Cultrone A, de Vos WM, Delorme C, Denariaraz G., Derrien M, Dervyn R, Feng Q, Grarup N, Guarner F, Guedon E, Haimet F, Jamet A, Juncker A, Juste C, Kennedy S, Khaci G, Kleerebezem M, Knoll J, Layec S, Leclerc M, Leonard P, LePaslier D, m'Rini C, Maguin E, Manichanh C, Mende D, Merieux A, Oozer R, Parkhill J, Pelletier E, POns N, QinJ, rasmussen S, Renault P, Rescigno M, Sanchez N, Sicheritz-Ponten T, Tap J, Tims S, Torrejon A, Turner K, van de Guchet M, van hylckama Vlieg JE, Vandemeulebrouck G, Varela E, Veiga P, Weissenbach J, Winogradski Y, Yamada T, Zoetendal EG; Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.