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 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 - 13 Jul 2016

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

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., 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, vol. 535, no. 7612, pp. 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.",

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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

Keywords

UN SDGs

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