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 Dore; Ismo Mattila; Damian Rafal Plichta; Paivi Poho; Lars Hellgren; Manimozhiyan Arumugam; Shinichi Sunagawa; Sara Vieira-Silva; Torben Jørgensen; Jacob Bak Holm; Kajetan Trost; Karsten Kristiansen; Susanne Brix Pedersen; Jeroen Raes; Jun Wang; Torben Hansen; Peer Bork; Søren Brunak; Matej Oresic; S. Dusko Ehrlich; Oluf Pedersen

doi:10.1038/nature18646

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 Dore, Ismo Mattila, Damian Rafal Plichta, Paivi Poho, Lars Hellgren, Manimozhiyan Arumugam, Shinichi Sunagawa, Sara Vieira-SilvaTorben Jørgensen, Jacob Bak Holm, Kajetan Trost, Karsten Kristiansen, Susanne Brix Pedersen, Jeroen Raes, Jun Wang, Torben Hansen, Peer Bork, Søren Brunak, Matej Oresic, S. Dusko Ehrlich, Oluf Pedersen

Research output: Contribution to journal › Journal article › Research › peer-review

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.

Original language	English
Journal	Nature
Volume	535
Issue number	7612
Pages (from-to)	376-381
Number of pages	20
ISSN	0028-0836
DOIs	https://doi.org/10.1038/nature18646
Publication status	Published - 2016

Keywords

Microbial genetics
Endocrine system and metabolic diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/nature18646

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Pedersen, H. K., Gudmundsdottir, V., Nielsen, H. B., Hyotylainen, T., Nielsen, T., Jensen, B. A. H., Forslund, K., Hildebrand, F., Prifti, E., Falony, G., Le Chatelier, E., Levenez, F., Dore, J., Mattila, I., Plichta, D. R., Poho, P., Hellgren, L., Arumugam, M., Sunagawa, S., ... Pedersen, O. (2016). Human gut microbes impact host serum metabolome and insulin sensitivity. Nature, 535(7612), 376-381. https://doi.org/10.1038/nature18646

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title = "Human gut microbes impact host serum metabolome and insulin sensitivity",

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.",

keywords = "Microbial genetics, Endocrine system and metabolic diseases",

author = "Pedersen, {Helle Krogh} and Valborg Gudmundsdottir and Nielsen, {Henrik Bj{\o}rn} and Tuulia Hyotylainen and Trine Nielsen and Jensen, {Benjamin A. H.} and Kristoffer Forslund and Falk Hildebrand and Edi Prifti and Gwen Falony and {Le Chatelier}, Emmanuelle and Florence Levenez and Joel Dore and Ismo Mattila and Plichta, {Damian Rafal} and Paivi Poho and Lars Hellgren and Manimozhiyan Arumugam and Shinichi Sunagawa and Sara Vieira-Silva and Torben J{\o}rgensen and Holm, {Jacob Bak} and Kajetan Trost and Karsten Kristiansen and Pedersen, {Susanne Brix} and Jeroen Raes and Jun Wang and Torben Hansen and Peer Bork and S{\o}ren Brunak and Matej Oresic and Ehrlich, {S. Dusko} and Oluf Pedersen",

year = "2016",

doi = "10.1038/nature18646",

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volume = "535",

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Pedersen, HK, Gudmundsdottir, V, Nielsen, HB, Hyotylainen, T, Nielsen, T, Jensen, BAH, Forslund, K, Hildebrand, F, Prifti, E, Falony, G, Le Chatelier, E, Levenez, F, Dore, J, Mattila, I, Plichta, DR, Poho, P, Hellgren, L, Arumugam, M, Sunagawa, S, Vieira-Silva, S, Jørgensen, T, Holm, JB, Trost, K, Kristiansen, K, Pedersen, SB, Raes, J, Wang, J, Hansen, T, Bork, P, Brunak, S, Oresic, M, Ehrlich, SD & Pedersen, O 2016, 'Human gut microbes impact host serum metabolome and insulin sensitivity', Nature, vol. 535, no. 7612, pp. 376-381. https://doi.org/10.1038/nature18646

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 A. H.

AU - Forslund, Kristoffer

AU - Hildebrand, Falk

AU - Prifti, Edi

AU - Falony, Gwen

AU - Le Chatelier, Emmanuelle

AU - Levenez, Florence

AU - Dore, Joel

AU - Mattila, Ismo

AU - Plichta, Damian Rafal

AU - Poho, Paivi

AU - Hellgren, Lars

AU - Arumugam, Manimozhiyan

AU - Sunagawa, Shinichi

AU - Vieira-Silva, Sara

AU - Jørgensen, Torben

AU - Holm, Jacob Bak

AU - Trost, Kajetan

AU - Kristiansen, Karsten

AU - Pedersen, Susanne Brix

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

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 - Microbial genetics

KW - Endocrine system and metabolic diseases

U2 - 10.1038/nature18646

DO - 10.1038/nature18646

M3 - Journal article

C2 - 27409811

SN - 0028-0836

VL - 535

SP - 376

EP - 381

JO - Nature

JF - Nature

IS - 7612

ER -

Human gut microbes impact host serum metabolome and insulin sensitivity

Abstract

Keywords

UN SDGs

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