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  • 1.
    Pedersen, Helle Krogh
    et al.
    Novo Nordisk Foundation Center for Protein Research, Disease Systems Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
    Gudmundsdottir, Valborg
    Center for Biological Sequence Analysis, Dept. of Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark.
    Nielsen, Henrik Bjorn
    Center for Biological Sequence Analysis, Dept. of Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology. Turku Centre for Biotechnology, Åbo Akademi University, Turku, Finland; Turku Centre for Biotechnology, University of Turku, Turku, Finland; VTT Technical Research Centre of Finland, Espoo, Finland.
    Nielsen, Trine
    Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Jensen, Benjamin A. H.
    Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
    Forslund, Kristoffer
    European Molecular Biology Laboratory, Heidelberg, Germany.
    Hildebrand, Falk
    European Molecular Biology Laboratory, Heidelberg, Germany; Department of Bioscience Engineering, Vrije Universiteit Brussel, Brussels, Belgium; Center for the Biology of Disease, VIB, Leuven, Belgium.
    Prifti, Edi
    MGP MetaGénoPolis, INRA, Université Paris-Saclay, Jouy en Josas, France; Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
    Falony, Gwen
    Center for the Biology of Disease, VIB, Leuven, Belgium; Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium.
    Le Chatelier, Emmanuelle
    MGP MetaGénoPolis, INRA, Université Paris-Saclay, Jouy en Josas, France.
    Levenez, Florence
    MGP MetaGénoPolis, INRA, Université Paris-Saclay, Jouy en Josas, France.
    Dore, Joel
    MGP MetaGénoPolis, INRA, Université Paris-Saclay, Jouy en Josas, France; Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
    Mattila, Ismo
    VTT Technical Research Centre of Finland, Espoo, Finland; Steno Diabetes Center, Gentofte, Denmark.
    Plichta, Damian R.
    Center for Biological Sequence Analysis, Dept. of Systems Biology, Technical University of Denmark, Kongens, Lyngby, Denmark.
    Pöhö, Paivi
    VTT Technical Research Centre of Finland, Espoo, Finland; Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
    Hellgren, Lars I.
    Center for Biological Sequence Analysis, Dept. of Systems Biology, Technical University of Denmark, Kongens, Lyngby, Denmark.
    Arumugam, Manimozhiyan
    Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Sunagawa, Shinichi
    European Molecular Biology Laboratory, Heidelberg, Germany; Institute of Microbiology, ETH Zurich, Zurich, Switzerland.
    Vieira-Silva, Sara
    Center for the Biology of Disease, VIB, Leuven, Belgium; Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium.
    Jørgensen, Torben
    Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Research Centre for Prevention and Health, Centre for Health, Capital Region, Glostrup Hospital, Glostrup, Denmark.
    Holm, Jacob Bak
    Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
    Trost, Kajetan
    Steno Diabetes Center, Gentofte, Denmark.
    Kristiansen, Karsten
    Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark; BGI-Shenzhen, Shenzhen, China.
    Brix, Susanne
    Center for Biological Sequence Analysis, Dept. of Systems Biology, Technical University of Denmark, Kongens, Lyngby, Denmark.
    Raes, Jeroen
    Department of Bioscience Engineering, Vrije Universiteit Brussel, Brussels, Belgium; Center for the Biology of Disease, VIB, Leuven, Belgium; Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium.
    Wang, Jun
    Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark; BGI-Shenzhen, Shenzhen, China; Princess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia; Macau University of Science and Technology, Taipa, China; Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong, China.
    Hansen, Torben
    Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
    Bork, Peer
    European Molecular Biology Laboratory, Heidelberg, Germany; Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, Heidelberg, Germany; Max Delbrück Centre for Molecular Medicine, Berlin, Germany; Department of Bioinformatics, University of Wuerzburg, Würzburg, Germany.
    Brunak, Søren
    Center for Biological Sequence Analysis, Dept. of Systems Biology, Technical University of Denmark, Kongens, Lyngby, Denmark; Novo Nordisk Foundation Center for Protein Research, Disease Systems Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Oresic, Matej
    Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland; VTT Technical Research Centre of Finland, Espoo, Finland; Steno Diabetes Center, Gentofte, Denmark.
    Ehrlich, S. Dusko
    Center for Biological Sequence Analysis, Dept. of Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark; University of Örebro, Örebro, Sweden.
    Pedersen, Oluf
    Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Human gut microbes impact host serum metabolome and insulin sensitivity2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 535, no 7612, p. 376-381Article in journal (Refereed)
    Abstract [en]

    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.

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