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Human gut microbes impact host serum metabolome and insulin sensitivity
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.
Center for Biological Sequence Analysis, Dept. of Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark.
Center for Biological Sequence Analysis, Dept. of Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark.
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.
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2016 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 535, no 7612, p. 376-381Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2016. Vol. 535, no 7612, p. 376-381
National Category
Endocrinology and Diabetes Microbiology
Identifiers
URN: urn:nbn:se:oru:diva-51849DOI: 10.1038/nature18646ISI: 000380344200031PubMedID: 27409811Scopus ID: 2-s2.0-84978081339OAI: oai:DiVA.org:oru-51849DiVA, id: diva2:956148
Note

Funding Agencies:

European Community HEALTH-F4-2007-201052

Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care (LuCamp), Metagenopolis grant ANR-11-DPBS-0001  HEALTH-F4-2012-305312

Rega institute for Medical Research, KU Leuven

Agency for Innovation by Science and Technology (IWT) 267139

Fund for Scientific Research Flanders (FWO)

Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research) 250114

EU FP7 Project TORNADO 222720

European Union 600375

Innovative Medicines Initiative Joint Undertaking from the European Union 115317

Available from: 2016-08-29 Created: 2016-08-29 Last updated: 2018-09-12Bibliographically approved

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Hyötyläinen, TuuliaSunagawa, ShinichiOresic, Matej

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