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; Karsten Kristiansen; Susanne Brix; Jeroen Raes; Jun Wang; Torben Hansen; Peer Bork; Søren Brunak; Matej Oresic; S Dusko Ehrlich; Oluf Pedersen; MetaHIT Consortium

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 Doré, Ismo Mattila, Damian R Plichta, Päivi Pöhö, Lars I Hellgren, Manimozhiyan Arumugam, Shinichi Sunagawa, Sara Vieira-SilvaTorben Jørgensen, Jacob Bak Holm, Kajetan Trošt, Karsten Kristiansen, Susanne Brix, Jeroen Raes, Jun Wang, Torben Hansen, Peer Bork, Søren Brunak, Matej Oresic, S Dusko Ehrlich, Oluf Pedersen, MetaHIT Consortium

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

1363 Citations (Scopus)

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	6
ISSN	0028-0836
DOIs	https://doi.org/10.1038/nature18646
Publication status	Published - 2016
Externally published	Yes

Keywords

Journal Article
Research Support, Non-U.S. Gov't

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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., Doré, J., Mattila, I., Plichta, D. R., Pöhö, P., Hellgren, L. I., Arumugam, M., Sunagawa, S., ... MetaHIT Consortium (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 = "Journal Article, Research Support, Non-U.S. Gov't",

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 Dor{\'e} and Ismo Mattila and Plichta, {Damian R} and P{\"a}ivi P{\"o}h{\"o} and Hellgren, {Lars I} and Manimozhiyan Arumugam and Shinichi Sunagawa and Sara Vieira-Silva and Torben J{\o}rgensen and Holm, {Jacob Bak} and Kajetan Tro{\v s}t and Karsten Kristiansen and 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 and {MetaHIT Consortium}",

year = "2016",

doi = "10.1038/nature18646",

language = "English",

volume = "535",

pages = "376--381",

journal = "Nature",

issn = "0028-0836",

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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, Doré, J, Mattila, I, Plichta, DR, Pöhö, P, Hellgren, LI, Arumugam, M, Sunagawa, S, Vieira-Silva, S, Jørgensen, T, Holm, JB, Trošt, K, Kristiansen, K, Brix, S, Raes, J, Wang, J, Hansen, T, Bork, P, Brunak, S, Oresic, M, Ehrlich, SD, Pedersen, O & MetaHIT Consortium 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 - 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

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 - Journal Article

KW - Research Support, Non-U.S. Gov't

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

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Keywords

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