Human gut microbes impact host serum metabolome and insulin sensitivity

: Helle Krogh Pedersen, Valborg Gudmundsdottir, Henrik Bjørn Nielsen, Tuulia Hyotylainen, Trine Nielsen, Benjamin A. H. Jensen, Kristoffer Forslund, Falk Hildebrand, Edi Prifti, Gwen Falony, Emmanuelle Le Chatelier, Florence Levenez, Joel Doré, Ismo Mattila, Damian R. Plichta, Päivi Pöhö, Lars I. Hellgren, Manimozhiyan Arumugam, Shinichi Sunagawa, Sara Vieira-Silva, Torben Jørgensen, Jacob Bak Holm, Kajetan Trošt, MetaHIT Consortium, Karsten Kristiansen, Susanne Brix, Jeroen Raes, Jun Wang, Torben Hansen, Peer Bork, Søren Brunak, Matej Oresic, S. Dusko Ehrlich, Oluf Pedersen

Publisher: NATURE PUBLISHING GROUP

: 2016

: Nature

: NATURE

: 535

: 7612

: 376

: 381

: 6

: 0028-0836

DOI: https://doi.org/10.1038/nature18646

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.