Human gut microbes impact host serum metabolome and insulin sensitivity

Helle Krogh Pedersen 1 Valborg Gudmundsdottir 2 Henrik Bjørn Nielsen 1 Tuulia Hyotylainen 3, 4, 5, 6 Trine Nielsen 7 Benjamin a H Jensen 8 Kristoffer Forslund 9 Falk Hildebrand 9, 10, 11 Edi Prifti 12, 13, 14 Gwen Falony 15, 16 Emmanuelle Le Chatelier 12 Florence Levenez 12 Joel Dore 17, 12 Ismo Mattila 6, 18 Damian R Plichta 1 Päivi Pöhö 6, 19 Lars I Hellgren 1 Manimozhiyan Arumugam 20 Shinichi Sunagawa 9, 21 Sara Vieira-Silva 22, 16 Torben Jørgensen 23, 24 Jacob Bak Holm 25 Kajetan Trošt 18 Karsten Kristiansen 8, 26 Susanne Brix 1 Jeroen Raes 27, 22, 16 Jun Wang 8, 26, 28, 29, 30 Torben Hansen 20, 31 Peer Bork 9, 32, 33, 34 Søren Brunak 1, 35 Matej Oresic 36, 4, 6, 18 S. Dusko Ehrlich 37, 38, 39, 40 Oluf Pedersen 20, 23 . Metahit Consortium Mathieu Almeida 17, 12 Jean-Michel Batto 17 Hervé Blottiere 17, 12 Antonietta Cultrone 17 Christine Delorme 17 Rozenn Dervyn 17 Eric Guedon 17 Florence Haimet 12, 17 Alexandre Jamet 17 Catherine Juste 17 Sean Kennedy 12, 17 Ghalia Kaci 17 Michiel Kleerebezem 41 Séverine Layec 42 Marion Leclerc 17 Pierre Léonard 12, 17 Emmanuelle Maguin 43 Chaysavanh Manichanh 44 Nicolas Pons 12, 17 Pierre Renault 17 Nicolas Sanchez 17 Maarten van de Guchte 17 Johan van Hylckama Vlieg 45 Gaetana Vandemeulebrouck 17 Yohanan Winogradsky 17
Abstract : 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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Helle Krogh Pedersen, Valborg Gudmundsdottir, Henrik Bjørn Nielsen, Tuulia Hyotylainen, Trine Nielsen, et al.. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature, Nature Publishing Group, 2016, 535 (7612), pp.376-381. ⟨10.1038/nature18646⟩. ⟨hal-01594855⟩

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