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1. Coculture fermentations of Bifidobacterium species and Bacteroides thetaiotaomicron reveal a mechanistic insight into the prebiotic effect of inulin-type fructans.

Author

Falony G, Calmeyn T, Leroy F, and De Vuyst L

Subjects
Coculture Techniques, Fermentation, Inulin metabolism, Oligosaccharides metabolism, Bacteroides growth & development, Bacteroides metabolism, Bifidobacterium growth & development, Bifidobacterium metabolism, Fructans metabolism
Abstract

Four bifidobacteria, each representing a cluster of strains with specific inulin-type-fructan degradation capacities, were grown in coculture fermentations with Bacteroides thetaiotaomicron LMG 11262, a strain able to metabolize both oligofructose and inulin. In a medium for colon bacteria with inulin as the sole added energy source, the ability of the bifidobacteria to compete for this substrate reflected phenotypical variation. Bifidobacterium breve Yakult, a strain that was not able to degrade oligofructose or inulin, was outcompeted by B. thetaiotaomicron LMG 11262. Bifidobacterium adolescentis LMG 10734, a strain that could degrade oligofructose (displaying a preferential breakdown mechanism) but that did not grow on inulin, managed to become competitive when oligofructose and short fractions of inulin started to accumulate in the fermentation medium. Bifidobacterium angulatum LMG 11039(T), a strain that was previously shown to degrade all oligofructose fractions simultaneously and to be able to partially break down inulin, was competitive from the beginning of the fermentation, consuming short fractions of inulin from the moment they appeared. Bifidobacterium longum LMG 11047, representing a cluster of bifidobacteria that shared both high fructose consumption and oligofructose degradation rates and were able to perform partial breakdown of inulin, was the dominating strain in a coculture with B. thetaiotaomicron LMG 11262. These observations indicate that distinct subgroups within the large-intestinal Bifidobacterium population will be stimulated by different groups of prebiotic inulin-type fructans, a variation that could be reflected in differences concerning their health-promoting effects.

Published
2009
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2. Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Author

Bel Lassen, Pierre, Nielsen, Trine, Bergh, Per-Olof, Rouault, Christine, André, Sébastien, Marquet, Florian, Andreelli, Fabrizio, Salem, Joe-Elie, Assmann, Karen, Bastard, Jean-Philippe, Forslund, Sofia, Le Chatelier, Emmanuelle, Falony, Gwen, Pons, Nicolas, Prifti, Edi, Quinquis, Benoit, Roume, Hugo, Vieira-Silva, Sara, Hansen, Tue, Pedersen, Helle Krogh, Lewinter, Christian, Sønderskov, Nadja, Vestergaard, Henrik, Raes, Jeroen, Nielsen, Jens, Bork, Peer, Ehrlich, S. Dusko, Pedersen, Oluf, Aron-Wisneswky, Judith, Clément, Karine, Bäckhed, Fredrik, Molinaro, Antonio, Lassen, Pierre, Henricsson, Marcus, Wu, Hao, Adriouch, Solia, Belda, Eugeni, Chakaroun, Rima, Nielse, Trine, Bergh, Christine, Rouault, Sébastien, Andr, Florian, Marquet, Fabrizio, Andreelli, Joe-Elie, Salem, Karen, Assmann, Jean-Philippe, Bastard, Sofia, Forslund, Emmanuelle, Le Chatelier, Gwen, Falon, Nicolas, Pons, Edi, Prift, Benoit, Quinquis, Hugo, Roume, Sara, Vieira-Silv, Tue, Hansen, Krogh, Pedersen, Christian, Lewinter, Nadja, The, Metacardis, Køber, Lars, Vestergaar, Henrik, Hansen, Torben, Zucker, Jean-Daniel, Galan, Pilar, Dumas, Marc-Emmanuel, Rae, Jeroen, Oppert, Jean-Michel, Letunic, Ivica, Nielse, Jens, Ehrlic, S, Stumvoll, Michael, Pederse, Oluf, Aron-Wisnewsky, Judith, Bäckhe, Fredrik, Sahlgrenska Center for Cardiovascular and Metabolic Research, Partenaires INRAE, Sahlgrenska University Hospital, Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche en Nutrition Humaine d'Ile-de-France (CRNH-IDF), Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Sorbonne Paris Nord, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université (SU), Medical Department III – Endocrinology, Nephrology, Rheumatology, Universität Leipzig [Leipzig], Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Centre d'Investigation Clinique de Paris Est, Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital Tenon [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Experimental and Clinical Research Center [Berlin, Germany], Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association-Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, Université Catholique de Louvain (UCL), VIB-KU Leuven Center for Microbiology [Belgium], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Sorbonne Université (SU)-Universtié Yaoundé 1 [Cameroun]-Université Cadi Ayyad [Marrakech] (UCA)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de la francophonie pour l'informatique-Institut de Recherche pour le Développement (IRD [France-Nord]), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Metabolism, Digestion and Reproduction, Imperial College London, National Heart and Lung Institute [London] (NHLI), Royal Brompton and Harefield NHS Foundation Trust-Imperial College London, Centre de Recherche en Nutrition Humaine - Ile de France (CRNH - IDF), Biobyte Solutions GMBH, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Sorbonne Paris Nord, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Sahlgrenska Academy at University of Gothenburg [Göteborg], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Helmholtz-Gemeinschaft = Helmholtz Association, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Rega Institute for Medical Research [Leuven, België], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD [France-Nord]), Chalmers University of Technology [Göteborg], European Molecular Biology Laboratory [Heidelberg] (EMBL), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, HAL-SU, Gestionnaire, Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord-Institut National Agronomique Paris-Grignon (INA P-G)-Sorbonne Université (SU)-CETAF-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut de Recherche pour le Développement (IRD [France-Nord])-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Université de Yaoundé I-Sorbonne Université (SU), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Auteur indépendant, Commission of the European Communities, and Universität Leipzig

Subjects
0301 basic medicine, Male, ACCURATE METHOD, endocrine system diseases, Metabolite, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Type 2 diabetes, GUT MICROBIOME, GLUCOSE, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, [CHIM] Chemical Sciences, Prediabetes, lcsh:Science, 2. Zero hunger, RISK, Multidisciplinary, biology, INSULIN SENSITIVITY, Imidazoles, HOMEOSTASIS MODEL ASSESSMENT, Middle Aged, 3. Good health, Multidisciplinary Sciences, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Science & Technology - Other Topics, Enterotype, Female, Adult, medicine.medical_specialty, Science, Carbohydrate metabolism, Microbiology, digestive system, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, INTESTINAL MICROBIOTA, Internal medicine, medicine, Humans, [CHIM]Chemical Sciences, Histidine, Author Correction, PHYSIOLOGY, Aged, Science & Technology, Bacteria, General Chemistry, Metabolism, medicine.disease, biology.organism_classification, Gastrointestinal Microbiome, MetaCardis Consortium, METAGENOME, INDIVIDUALS, 030104 developmental biology, chemistry, Diabetes Mellitus, Type 2, Cardiovascular and Metabolic Diseases, lcsh:Q, Bacteroides
Abstract

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism., Gut microbial metabolism of nutrients contributes to metabolic diseases, and the histidine metabolite imidazole propionate (ImP) is produced by type 2 diabetes (T2D) associated microbiome. Here the authors report that circulating ImP levels are increased in subjects with prediabetes or T2D in three European populations, and this increase associates with altered gut microbiota rather than dietary histidine.

Published
2020

3. Human gut microbes impact host serum metabolome and insulin sensitivity

Author

Pedersen, Helle Krogh, Gudmundsdottir, Valborg, Nielsen, Henrik Bjørn, Hyotylainen, Tuulia, Nielsen, Trine, Jensen, Benjamin A H, Forslund, Kristoffer, Hildebrand, Falk, Prifti, Edi, Falony, Gwen, Le Chatelier, Emmanuelle, Levenez, Florence, Dore, Joel, Mattila, Ismo, Plichta, Damian R, Pöhö, Päivi, Hellgren, Lars I, Arumugam, Manimozhiyan, Sunagawa, Shinichi, Vieira-Silva, Sara, Jørgensen, Torben, Holm, Jacob Bak, Trošt, Kajetan, Kristiansen, Karsten, Brix, Susanne, Raes, Jeroen, Wang, Jun, Hansen, Torben, Bork, Peer, Brunak, Søren, Oresic, Matej, Ehrlich, S. Dusko, Pedersen, Oluf, MetaHIT Consortium, ., Almeida, Mathieu, Batto, Jean-Michel, Blottiere, Hervé, Cultrone, Antonietta, Delorme, Christine, Dervyn, Rozenn, Guedon, Eric, Haimet, Florence, Jamet, Alexandre, Juste, Catherine, Kennedy, Sean, Kaci, Ghalia, Kleerebezem, Michiel, Layec, Séverine, Leclerc, Marion, Léonard, Pierre, Maguin, Emmanuelle, Manichanh, Chaysavanh, Pons, Nicolas, Renault, Pierre, Sanchez, Nicolas, Van De Guchte, Maarten, Van Hylckama Vlieg, Johan, Vandemeulebrouck, Gaetana, Winogradsky, Yohanan, Center for Biological Sequence Analysis - Department of Systems Biology, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), University of Denmark, Turku Centre for Biotechnology, University of Turku-Åbo Academy University, Åbo Akademi University [Turku], Örebro University, VTT Technical Research Centre of Finland (VTT), Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Laboratory of Genomics and Molecular Biomedicine - Department of Biology, University of Copenhagen = Københavns Universitet (UCPH), European Molecular Biology Laboratory, Department of Bioscience Engineering, University of Antwerp (UA), Center for the Biology of Disease, VIB, MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centter for the Biology of Disease, Department of Microbiology and Immunology, Rega Institute for Medical Research, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Steno Diabetes Center, Faculty of Pharmacy, University of Valencia, Institute of Microbiology, Université de Lausanne = University of Lausanne (UNIL), Centre for the Biology of Disease, Research Centre for Prevention and Health - Centre for Health, Glostrup Hospital, Beijing Genomics Institute [Shenzhen] (BGI), Vrije Universiteit Brussel [Bruxelles] (VUB), Princess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Macau University of Science and Technology (MUST), Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Faculty of Health Sciences, Aarhus University [Aarhus], Molecular Medicine Partnership Unit, Heidelberg University, Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Department of Bioinformatics, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Disease Systems Biology [Copenhagen], Novo Nordisk Foundation Center for Protein Research (CPR), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Health and Medical Sciences, Centre for Biotechnology, Silesian University of Technology, Université Paris-Saclay, Centre for Host–Microbiome Interactions - Dental Institute Central Office, King‘s College London, Guys Hospital, Génie et Microbiologie des Procédés Alimentaires (GMPA), Département Microbiologie et Chaîne Alimentaire (MICA), Danone Research, Groupe Danone, International Human Microbiome Standards [FP7-HEALTH-2010-261376], Metagenopolis [ANR-11-DPBS-0001], Novo Nordisk Foundation, Lundbeck Foundation, European Project: 222720,EC | FP7 | SP1 | KBBE ,FP7-KBBE-2007-2A,TORNADO(2009), Technical University of Denmark [Lyngby] (DTU), University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), University of Copenhagen = Københavns Universitet (KU), Jouy-en-Josas, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], Université de Lausanne (UNIL), BGI Shenzhen, Vrije University, University of Heidelberg, Max Delbrück Center for Molecular Medicine, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Health and Medical Sciences, US 1367 MGP MetaGénoPolis, Laboratory of Microbiology, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Digestive System Research Unit, Vall d'Hebron University Hospital [Barcelona], European Project: 201052, Faculty of Sciences and Bioengineering Sciences, Microbial Interactions, Department of Bio-engineering Sciences, and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
0301 basic medicine, Male, [SDV]Life Sciences [q-bio], Prevotella, Gastrointestinal Microbiome/physiology, Bacteroides/physiology, Type 2 diabetes, Fasting/blood, SERUM, Mice, 0302 clinical medicine, insulin resistance, Bacteroides, Netherlands, Multidisciplinary, biology, Research Support, Non-U.S. Gov't, Gastrointestinal Microbiome, Prevotella/physiology, Fasting, 3. Good health, Cardiovascular diseases, Cardiovascular Diseases/metabolism, Metabolome, Amino Acids, Branched-Chain/biosynthesis, medicine.medical_specialty, Glyco-Forum Section, Serum/metabolism, mice, 030209 endocrinology & metabolism, metagenome, 03 medical and health sciences, Insulin resistance, Internal medicine, Glucose Intolerance, medicine, Animals, Humans, Microbiome, Glucose Intolerance/blood, ta1182, biology.organism_classification, medicine.disease, Obesity, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, Metagenome, Insulin Resistance, Amino Acids, Branched-Chain
Abstract

MetaHIT Consortium: Almeida M, Antolin M, Artiguenave F, Batto JM, Bertalan M, Blottiere H, Boruel N, Brechot C, Bruls T, Burgdorf K, Casellas F, Cultrone A, de Vos WM, Delorme C, Denariaraz G., Derrien M, Dervyn R, Feng Q, Grarup N, Guarner F, Guedon E, Haimet F, Jamet A, Juncker A, Juste C, Kennedy S, Khaci G, Kleerebezem M, Knoll J, Layec S, Leclerc M, Leonard P, LePaslier D, m'Rini C, Maguin E, Manichanh C, Mende D, Merieux A, Oozer R, Parkhill J, Pelletier E, POns N, QinJ, rasmussen S, Renault P, Rescigno M, Sanchez N, Sicheritz-Ponten T, Tap J, Tims S, Torrejon A, Turner K, van de Guchet M, van hylckama Vlieg JE, Vandemeulebrouck G, Varela E, Veiga P, Weissenbach J, Winogradski Y, Yamada T, Zoetendal EG; 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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