Human gut microbes impact host serum metabolome and insulin sensitivity

Pedersen, Helle Krogh; Gudmundsdottir, Valborg; Nielsen, Henrik Bjørn; Hyotylainen, Tuulia; Nielsen, Trine; Jensen, Benjamin AH; Forslund, Kristoffer; Hildebrand, Falk; Prifti, Edi; Falony, Gwen; Le Chatelier, Emmanuelle; Levenez, Florence; Doré, 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; Consortium, MetaHIT; Kristiansen, Karsten; Brix, Susanne; Raes, Jeroen; Wang, Jun; Hansen, Torben; Bork, Peer; Brunak, Søren; Oresic, Matej; Ehrlich, S Dusko; Pedersen, Oluf

doi:10.1038/nature18646

Human gut microbes impact host serum metabolome and insulin sensitivity

Author:

Pedersen, Helle Krogh

Gudmundsdottir, Valborg ; Nielsen, Henrik Bjørn ; Hyotylainen, Tuulia ; Nielsen, Trine ; Jensen, Benjamin AH ; Forslund, Kristoffer ; Hildebrand, Falk ; Prifti, Edi ; Falony, Gwen ; Le Chatelier, Emmanuelle ; Levenez, Florence ; Doré, 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 ; Consortium, MetaHIT ; Kristiansen, Karsten ; Brix, Susanne ; Raes, Jeroen ; Wang, Jun ; Hansen, Torben ; Bork, Peer ; Brunak, Søren ; Oresic, Matej ; Ehrlich, S Dusko ; Pedersen, Oluf

Keywords:

Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, SATURATED FATTY-ACIDS, CHAIN AMINO-ACIDS, RESISTANCE, GLUCOSE, ASSOCIATION, METAGENOME, ADIPOCYTE, ABUNDANCE, PROFILES, GENOMES, Amino Acids, Branched-Chain, Animals, Bacteroides, Cardiovascular Diseases, Fasting, Gastrointestinal Microbiome, Glucose Intolerance, Humans, Insulin Resistance, Male, Metabolome, Metagenome, Mice, Mice, Inbred C57BL, Netherlands, Prevotella, Serum, MetaHIT Consortium, General Science & Technology

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.