1. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota
- Author
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Forslund, Kristoffer, Hildebrand, Falk, Nielsen, Trine, Falony, Gwen, Le Chatelier, Emmanuelle, Sunagawa, Shinichi, Prifti, Edi, Vieira-Silva, Sara, Gudmundsdottir, Valborg, Pedersen, Helle Krogh, Arumugam, Manimozhiyan, Kristiansen, Karsten, Voigt, Anita Yvonne, Vestergaard, Henrik, Hercog, Rajna, Costea, Paul Igor, Kultima, Jens Roat, Li, Junhua, Jorgensen, Torben, Levenez, Florence, Dore, Joel, Consortium, MetaHit, Nielsen, H. Bjorn, Brunak, Soren, Raes, Jeroen, Hansen, Torben, Wang, Jun, Ehrlich, Dusko S, Bork, Peer, Pedersen, Oluf, Almeida, Mathieu, Batto, Jean-Michel, Blottiere, Hervé H, Cultrone, Antonietta, Delorme, Christine, derwyn, rozenn, Guédon, Eric, Haimet, Florence, Jamet, Alexandre, Juste, Catherine, Kennedy, Sean P., Kaci, Ghalia, Layec, Séverine, Leclerc, Marion, Léonard, Pierre, Maguin, Emmanuelle, Pons, Nicolas, Renault, Pierre, Sanchez, Nicolas, Van De Guchte, Maarten, Van Hylckama Vlieg, Johan, Vandemeulebrouck, Gaetana, Winogradsky, Yohanan, Structural and Computational Biology Unit, European Molecular Biology Laboratory [Hamburg] (EMBL), VIB Center for the Biology of Disease, Université Catholique de Louvain = Catholic University of Louvain (UCL), Department of Bioscience Engineering, Vrije Universiteit Brussel (VUB), 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), Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), 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) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark [Lyngby] (DTU), Department of Biology [Copenhagen], Faculty of Science [Copenhagen], Molecular Medicine Partnership Unit, Heidelberg University, Department of Applied Tumor Biology, Institute of Pathology, Beijing Genomics Institute [Shenzhen] (BGI), Faculty of Medicine, Aalborg University [Denmark] (AAU), Research Centre for Prevention and Health, Capital Region of Denmark, Department of Public Health [Copenhagen], Disease Systems Biology [Copenhagen], Novo Nordisk Foundation Center for Protein Research (CPR), University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Health and Medical Sciences, Faculty of Health Sciences, University of Southern Denmark (SDU), Macau University of Science and Technology (MUST), Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong (HKU), Princess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Centre for Host-Microbiome Interactions, Dental Institute Central Office, Guy’s Hospital, King‘s College London, Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Department of Bioinformatics, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Génie et Microbiologie des Procédés Alimentaires (GMPA), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Département Microbiologie et Chaîne Alimentaire (MICA), Metagenopolis grant ANR-11-DPBS-0001, European Research Council 268985, European Union 600375, Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care (LuCamp), Novo Nordisk Foundation NNF14CC0001, European Molecular Biology Laboratory (EMBL), Novo Nordisk Foundation, Innovation Fund Denmark through the MicrobDiab project, European Project: 201052, Faculty of Sciences and Bioengineering Sciences, Department of Bio-engineering Sciences, Microbiology, Université Catholique de Louvain, Vrije Universiteit [Brussels] (VUB), 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], University of Heidelberg, Beijing Genomics Institute, Max Delbrück Center for Molecular Medicine, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), 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)-Sorbonne Université (SU)-Sorbonne Université (SU), Danmarks Tekniske Universitet = Technical University of Denmark (DTU), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Health and Medical Sciences, and Julius-Maximilians-Universität Würzburg (JMU)
- Subjects
Male ,Diabetes Mellitus, Type 2/drug therapy ,endocrine system diseases ,GENOMES ,CLOSTRIDIUM ,Biology ,Microbiology ,DISEASE ,Article ,GLUCOSE ,Hypoglycemic Agents/pharmacology ,Metformin/pharmacology ,RNA, Ribosomal, 16S ,Nondestructive testing ,Forensic engineering ,Hypoglycemic Agents ,risk factors ,Humans ,Gastrointestinal Microbiome/drug effects ,Metagenome/drug effects ,RNA, Ribosomal, 16S/genetics ,Multidisciplinary ,IDENTIFICATION ,SEQUENCES ,business.industry ,Biodiversity ,CANCER ,Metformin ,Computational biology and bioinformatics ,3. Good health ,Gastrointestinal Microbiome ,METAGENOME ,Diabetes Mellitus, Type 2 ,SP-NOV ,Female ,HEALTH ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported. In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis. Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa. These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gut microbiota signatures of specific human diseases from those of medication. ispartof: Nature vol:528 issue:7581 pages:262-6 ispartof: location:England status: published
- Published
- 2015
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