Human gut microbes impact host serum metabolome and insulin sensitivity
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Human gut microbes impact host serum metabolome and insulin sensitivity. / Pedersen, Helle Krogh; Gudmundsdottir, Valborg; Nielsen, Henrik Bjørn; Hyotylainen, Tuulia; Nielsen, Trine; Jensen, Benjamin Anderschou Holbech; 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; Kristiansen, Karsten; Brix, Susanne; Raes, Jeroen; Wang, Jun; Hansen, Torben; Bork, Peer; Brunak, Søren; Oresic, Matej; Ehrlich, S Dusko; Pedersen, Oluf Borbye; MetaHIT Consortium.
In: Nature, Vol. 535, No. 7612, 2016, p. 376-381.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - Human gut microbes impact host serum metabolome and insulin sensitivity
AU - Pedersen, Helle Krogh
AU - Gudmundsdottir, Valborg
AU - Nielsen, Henrik Bjørn
AU - Hyotylainen, Tuulia
AU - Nielsen, Trine
AU - Jensen, Benjamin Anderschou Holbech
AU - Forslund, Kristoffer
AU - Hildebrand, Falk
AU - Prifti, Edi
AU - Falony, Gwen
AU - Le Chatelier, Emmanuelle
AU - Levenez, Florence
AU - Doré, Joel
AU - Mattila, Ismo
AU - Plichta, Damian R.
AU - Pöhö, Päivi
AU - Hellgren, Lars I.
AU - Arumugam, Manimozhiyan
AU - Sunagawa, Shinichi
AU - Vieira-Silva, Sara
AU - Jørgensen, Torben
AU - Holm, Jacob Bak
AU - Trošt, Kajetan
AU - Kristiansen, Karsten
AU - Brix, Susanne
AU - Raes, Jeroen
AU - Wang, Jun
AU - Hansen, Torben
AU - Bork, Peer
AU - Brunak, Søren
AU - Oresic, Matej
AU - Ehrlich, S Dusko
AU - Pedersen, Oluf Borbye
AU - MetaHIT Consortium
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Amino Acids, Branched-Chain
KW - Animals
KW - Bacteroides
KW - Cardiovascular Diseases
KW - Fasting
KW - Gastrointestinal Microbiome
KW - Glucose Intolerance
KW - Humans
KW - Insulin Resistance
KW - Male
KW - Metabolome
KW - Metagenome
KW - Mice
KW - Mice, Inbred C57BL
KW - Prevotella
KW - Serum
U2 - 10.1038/nature18646
DO - 10.1038/nature18646
M3 - Journal article
C2 - 27409811
VL - 535
SP - 376
EP - 381
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7612
ER -
ID: 166057145