Human gut microbes impact host serum metabolome and insulin sensitivity
Helle Krogh Pedersen
(1)
,
Valborg Gudmundsdottir
(2)
,
Henrik Bjørn Nielsen
(1)
,
Tuulia Hyotylainen
(3, 4, 5, 6)
,
Trine Nielsen
(7)
,
Benjamin a H Jensen
(8)
,
Kristoffer Forslund
(9)
,
Falk Hildebrand
(9, 10, 11)
,
Edi Prifti
(12, 13)
,
Gwen Falony
(14, 15)
,
Emmanuelle Le Chatelier
(12)
,
Florence Levenez
(12)
,
Joel Dore
(16, 12)
,
Ismo Mattila
(6, 17)
,
Damian R Plichta
(1)
,
Päivi Pöhö
(6, 18)
,
Lars I Hellgren
(1)
,
Manimozhiyan Arumugam
(7)
,
Shinichi Sunagawa
(9, 19)
,
Sara Vieira-Silva
(20, 15)
,
Torben Jørgensen
(21, 22)
,
Jacob Bak Holm
(7)
,
Kajetan Trošt
(17)
,
Metahit Consortium
,
Karsten Kristiansen
(8, 23)
,
Susanne Brix
(1)
,
Jeroen Raes
(24, 20, 15)
,
Jun Wang
(8, 23, 25, 26, 27)
,
Torben Hansen
(7, 28)
,
Peer Bork
(9, 29, 30, 31)
,
Søren Brunak
(1, 32)
,
Matej Oresic
(33, 4, 6, 17)
,
S. Dusko Ehrlich
(12, 34, 35, 36)
,
Oluf Pedersen
(7, 21)
,
Mathieu Almeida
(16, 12)
,
Jean-Michel Batto
(16)
,
Hervé Blottiere
(16, 12)
,
Antonietta Cultrone
(16)
,
Christine Delorme
(16)
,
Rozenn Dervyn
(16)
,
Eric Guédon
(16)
,
Florence Haimet
(12)
,
Alexandre Jamet
(16)
,
Catherine Juste
(16)
,
Sean Kennedy
(16)
,
Ghalia Kaci
(16)
,
Séverine Layec
(37)
,
Marion Leclerc
(16)
,
Pierre Léonard
(12)
,
Emmanuelle Maguin
(38)
,
Nicolas Pons
(12)
,
Pierre Renault
(16)
,
Nicolas Sanchez
(16)
,
Maarten van de Guchte
(16)
,
Johan van Hylckama Vlieg
(39)
,
Gaetana Vandemeulebrouck
(16)
,
Yohanan Winogradsky
(16)
1
Center for Biological Sequence Analysis - Department of Systems Biology
2 Center for Biological Sequence Analysis - Department of Systems Biology
3 Turku Centre for Biotechnology
4 Åbo Akademi University [Turku]
5 Örebro University
6 VTT - VTT Technical Research Centre of Finland
7 CBMR - Novo Nordisk Foundation Center for Basic Metabolic Research
8 Laboratory of Genomics and Molecular Biomedicine - Department of Biology
9 European Molecular Biology Laboratory
10 Department of Bioscience Engineering
11 Center for the Biology of Disease
12 MetaGenoPolis
13 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
14 Centter for the Biology of Disease
15 Department of Microbiology, Immunology and Transplantation [KU Leuven]
16 MICALIS - MICrobiologie de l'ALImentation au Service de la Santé
17 Steno Diabetes Center
18 Faculty of Pharmacy
19 Institute of Microbiology
20 Centre for the Biology of Disease
21 Faculty of Health and Medical Sciences
22 Research Centre for Prevention and Health - Centre for Health
23 BGI - Beijing Genomics Institute [Shenzhen]
24 Department of Bioscience Engineering
25 Princess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders
26 MUST - Macau University of Science and Technology
27 Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology
28 Faculty of Health Sciences
29 Molecular Medicine Partnership Unit
30 MDC - Max Delbrück Center for Molecular Medicine [Berlin]
31 Department of Bioinformatics
32 Disease Systems Biology [Copenhagen]
33 Centre for Biotechnology
34 Université Paris-Saclay
35 Centre for Host–Microbiome Interactions - Dental Institute Central Office
36 Guys Hospital
37 GMPA - Génie et Microbiologie des Procédés Alimentaires
38 MICA - Département Microbiologie et Chaîne Alimentaire
39 Danone Research
2 Center for Biological Sequence Analysis - Department of Systems Biology
3 Turku Centre for Biotechnology
4 Åbo Akademi University [Turku]
5 Örebro University
6 VTT - VTT Technical Research Centre of Finland
7 CBMR - Novo Nordisk Foundation Center for Basic Metabolic Research
8 Laboratory of Genomics and Molecular Biomedicine - Department of Biology
9 European Molecular Biology Laboratory
10 Department of Bioscience Engineering
11 Center for the Biology of Disease
12 MetaGenoPolis
13 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
14 Centter for the Biology of Disease
15 Department of Microbiology, Immunology and Transplantation [KU Leuven]
16 MICALIS - MICrobiologie de l'ALImentation au Service de la Santé
17 Steno Diabetes Center
18 Faculty of Pharmacy
19 Institute of Microbiology
20 Centre for the Biology of Disease
21 Faculty of Health and Medical Sciences
22 Research Centre for Prevention and Health - Centre for Health
23 BGI - Beijing Genomics Institute [Shenzhen]
24 Department of Bioscience Engineering
25 Princess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders
26 MUST - Macau University of Science and Technology
27 Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology
28 Faculty of Health Sciences
29 Molecular Medicine Partnership Unit
30 MDC - Max Delbrück Center for Molecular Medicine [Berlin]
31 Department of Bioinformatics
32 Disease Systems Biology [Copenhagen]
33 Centre for Biotechnology
34 Université Paris-Saclay
35 Centre for Host–Microbiome Interactions - Dental Institute Central Office
36 Guys Hospital
37 GMPA - Génie et Microbiologie des Procédés Alimentaires
38 MICA - Département Microbiologie et Chaîne Alimentaire
39 Danone Research
Trine Nielsen
- Fonction : Auteur
- PersonId : 770024
- ORCID : 0000-0002-2066-7895
Edi Prifti
- Fonction : Auteur
- PersonId : 1151183
- IdHAL : edi-prifti
- ORCID : 0000-0001-8861-1305
- IdRef : 155572822
Emmanuelle Le Chatelier
- Fonction : Auteur
- PersonId : 737756
- IdHAL : emmanuelle-le-chatelier
- ORCID : 0000-0002-2724-0536
Manimozhiyan Arumugam
- Fonction : Auteur
- PersonId : 770023
- ORCID : 0000-0002-0886-9101
Sara Vieira-Silva
- Fonction : Auteur
- PersonId : 775753
- ORCID : 0000-0002-4616-7602
Metahit Consortium
- Fonction : Auteur
Karsten Kristiansen
- Fonction : Auteur
- PersonId : 757952
- ORCID : 0000-0002-6024-0917
Susanne Brix
- Fonction : Auteur
- PersonId : 784036
- ORCID : 0000-0001-8951-6705
Jun Wang
- Fonction : Auteur
- PersonId : 881572
Torben Hansen
- Fonction : Auteur
- PersonId : 758676
- ORCID : 0000-0001-8748-3831
Matej Oresic
- Fonction : Auteur
- PersonId : 764512
- ORCID : 0000-0002-2856-9165
S. Dusko Ehrlich
- Fonction : Auteur
- PersonId : 1068832
- ORCID : 0000-0002-7563-4046
Oluf Pedersen
- Fonction : Auteur
- PersonId : 1070332
Mathieu Almeida
- Fonction : Collaborateur
Hervé Blottiere
- Fonction : Collaborateur
- PersonId : 747227
- IdHAL : herve-blottiere
- ORCID : 0000-0002-8390-0607
- IdRef : 076955648
Christine Delorme
- Fonction : Collaborateur
- PersonId : 736589
- IdHAL : christine-delorme
- ORCID : 0000-0002-5208-7238
- IdRef : 124303129
Eric Guédon
- Fonction : Collaborateur
- PersonId : 743950
- IdHAL : eguedon35
- ORCID : 0000-0002-0901-4447
- IdRef : 140101888
Alexandre Jamet
- Fonction : Collaborateur
- PersonId : 737690
- IdHAL : alexandre-jamet
- IdRef : 253129699
Sean Kennedy
- Fonction : Collaborateur
- PersonId : 1203215
Séverine Layec
- Fonction : Collaborateur
- PersonId : 754110
- IdHAL : severine-layec
- ORCID : 0000-0001-5053-8712
Marion Leclerc
- Fonction : Collaborateur
- PersonId : 748825
- IdHAL : marion-leclerc
- ORCID : 0000-0001-8684-2847
- IdRef : 142653721
Emmanuelle Maguin
- Fonction : Collaborateur
- PersonId : 751613
- IdHAL : e-maguin
- ORCID : 0000-0001-5452-3382
- IdRef : 032881487
Maarten van de Guchte
- Fonction : Collaborateur
- PersonId : 735862
- IdHAL : maarten-van-de-guchte
- ORCID : 0000-0002-5980-4631
Gaetana Vandemeulebrouck
- Fonction : Collaborateur
- PersonId : 969463
Résumé
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 vulgatusare 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.