Human gut microbes impact host serum metabolome and insulin sensitivity

Helle Krogh Pedersen; Valborg Gudmundsdottir; Henrik Bjørn Nielsen; Tuulia Hyotylainen; Trine Nielsen; Benjamin Anderschou Holbech 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 Borbye 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 Anderschou Holbech 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 Borbye Pedersen, MetaHIT Consortium

699 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Nature
Vol/bind	535
Udgave nummer	7612
Sider (fra-til)	376-381
Antal sider	6
ISSN	0028-0836
DOI	https://doi.org/10.1038/nature18646
Status	Udgivet - 13 jul. 2016

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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

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, OB & MetaHIT Consortium 2016, 'Human gut microbes impact host serum metabolome and insulin sensitivity', Nature, bind 535, nr. 7612, s. 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 = "Amino Acids, Branched-Chain, Animals, Bacteroides, Cardiovascular Diseases, Fasting, Gastrointestinal Microbiome, Glucose Intolerance, Humans, Insulin Resistance, Male, Metabolome, Metagenome, Mice, Mice, Inbred C57BL, Prevotella, Serum",

author = "Pedersen, {Helle Krogh} and Valborg Gudmundsdottir and Nielsen, {Henrik Bj{\o}rn} and Tuulia Hyotylainen and Trine Nielsen and Jensen, {Benjamin Anderschou Holbech} 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 Pedersen, {Oluf Borbye} and {MetaHIT Consortium}",

year = "2016",

month = jul,

day = "13",

doi = "10.1038/nature18646",

language = "English",

volume = "535",

pages = "376--381",

journal = "Nature",

issn = "0028-0836",

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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 - 2016/7/13

Y1 - 2016/7/13

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

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

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