Human gut microbes impact host serum metabolome and insulin sensitivity

被引：1617

作者：

Pedersen, Helle Krogh ^{[1
]}

Gudmundsdottir, Valborg ^{[1
]}

Nielsen, Henrik Bjorn ^{[1
]}

Hyotylainen, Tuulia ^{[2
,3
,4
,5
]}

Nielsen, Trine ^{[6
]}

Jensen, Benjamin A. H. ^{[7
]}

Forslund, Kristoffer ^{[8
]}

Hildebrand, Falk ^{[8
,9
,10
]}

Prifti, Edi ^{[11
,12
]}

Falony, Gwen ^{[10
,13
]}

Le Chatelier, Emmanuelle ^{[11
]}

Levenez, Florence ^{[11
]}

Dore, Joel ^{[11
,14
]}

Mattila, Ismo ^{[5
,15
]}

Plichta, Damian R. ^{[1
]}

Poho, Paivi ^{[5
,16
]}

Hellgren, Lars I. ^{[1
]}

Arumugam, Manimozhiyan ^{[6
]}

Sunagawa, Shinichi ^{[8
,17
]}

Vieira-Silva, Sara ^{[10
,13
]}

Jorgensen, Torben ^{[18
,19
]}

Holm, Jacob Bak ^{[7
]}

Trost, Kajetan ^{[15
]}

Kristiansen, Karsten ^{[7
,20
]}

Brix, Susanne ^{[1
]}

Raes, Jeroen ^{[9
,10
,13
]}

Wang, Jun ^{[7
,20
,21
,22
,23
,24
]}

Hansen, Torben ^{[6
,25
]}

Bork, Peer ^{[8
,26
,27
,28
,29
]}

Brunak, Soren ^{[1
,30
]}

Oresic, Matej ^{[3
,4
,5
,15
]}

Ehrlich, S. Dusko ^{[11
,31
]}

Pedersen, Oluf ^{[6
,18
]}

机构：

[1] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark

[2] Univ Orebro, SE-70281 Orebro, Sweden

[3] Univ Turku, Turku Ctr Biotechnol, FI-20520 Turku, Finland

[4] Abo Akad Univ, FI-20520 Turku, Finland

[5] VTT Tech Res Ctr Finland, FI-02044 Espoo, Finland

[6] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark

[7] Univ Copenhagen, Dept Biol, Lab Genom & Mol Biomed, DK-2100 Copenhagen, Denmark

[8] European Mol Biol Lab, D-69117 Heidelberg, Germany

[9] Vrije Univ Brussel, Dept Biosci Engn, B-1050 Brussels, Belgium

[10] VIB, Ctr Biol Dis, B-3000 Louvain, Belgium

[11] Univ Paris Saclay, INRA, MGP MetaGenoPolis, F-78350 Jouy En Josas, France

[12] Inst Cardiometab & Nutr ICAN, F-75013 Paris, France

[13] Katholieke Univ Leuven, Rega Inst, Dept Microbiol & Immunol, B-3000 Louvain, Belgium

[14] Univ Paris Saclay, INRA, AgroParisTech, Micalis Inst, F-78350 Jouy En Josas, France

[15] Steno Diabet Ctr, DK-2820 Gentofte, Denmark

[16] Univ Helsinki, Fac Pharm, FI-00014 Helsinki, Finland

[17] ETH, Inst Microbiol, CH-8092 Zurich, Switzerland

[18] Univ Copenhagen, Fac Hlth & Med Sci, DK-2200 Copenhagen, Denmark

[19] Glostrup Cty Hosp, Capital Reg, Ctr Hlth, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark

[20] BGI Shenzhen, Shenzhen 518083, Peoples R China

[21] King Abdulaziz Univ, Princess Al Jawhara Albrahim Ctr Excellence Res H, Jeddah, Saudi Arabia

[22] Macau Univ Sci & Technol, Ave Wai Long, Taipa, Macau, Peoples R China

[23] Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China

[24] Univ Hong Kong, State Key Lab Pharmaceut Biotechnol, Hong Kong, Hong Kong, Peoples R China

[25] Univ Southern Denmark, Fac Hlth Sci, DK-5000 Odense, Denmark

[26] Heidelberg Univ, Mol Med Partnership Unit, D-69120 Heidelberg, Germany

[27] European Mol Biol Lab, D-69120 Heidelberg, Germany

[28] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany

[29] Univ Wurzburg, Dept Bioinformat, D-97074 Wurzburg, Germany

[30] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Prot Res Dis Syst Biol, DK-2200 Copenhagen, Denmark

[31] Kings Coll London, Ctr Host Microbiome Interact, Dent Inst Cent Off, Guys Hosp, London SE1 9RT, England

来源：

NATURE | 2016年 / 535卷 / 7612期

基金：

芬兰科学院;

关键词：

SATURATED FATTY-ACIDS; CHAIN AMINO-ACIDS; RESISTANCE; GLUCOSE; ASSOCIATION; METAGENOME; ADIPOCYTE; ABUNDANCE; PROFILES; GENOMES;

D O I：

10.1038/nature18646

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：376 / +

页数：20

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