Publication Date:
2015-12-04
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681099/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681099/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Forslund, Kristoffer -- Hildebrand, Falk -- Nielsen, Trine -- Falony, Gwen -- Le Chatelier, Emmanuelle -- Sunagawa, Shinichi -- Prifti, Edi -- Vieira-Silva, Sara -- Gudmundsdottir, Valborg -- Krogh Pedersen, Helle -- Arumugam, Manimozhiyan -- Kristiansen, Karsten -- Voigt, Anita Yvonne -- Vestergaard, Henrik -- Hercog, Rajna -- Igor Costea, Paul -- Kultima, Jens Roat -- Li, Junhua -- Jorgensen, Torben -- Levenez, Florence -- Dore, Joel -- MetaHIT consortium -- Nielsen, H Bjorn -- Brunak, Soren -- Raes, Jeroen -- Hansen, Torben -- Wang, Jun -- Ehrlich, S Dusko -- Bork, Peer -- Pedersen, Oluf -- England -- Nature. 2015 Dec 10;528(7581):262-6. doi: 10.1038/nature15766. Epub 2015 Dec 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany. ; VIB Center for the Biology of Disease, Katholieke Universiteit Leuven, 3000 Leuven, Belgium. ; Department of Bioscience Engineering, Vrije Universiteit Brussel, 1040 Brussels, Belgium. ; The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. ; Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium. ; MICALIS, Institut National de la Recherche Agronomique, 78352 Jouy en Josas, France. ; Metagenopolis, Institut National de la Recherche Agronomique, 78352 Jouy en Josas, France. ; Institute of Cardiometabolism and Nutrition, 75013 Paris, France. ; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, 2800 Kongens Lyngby, Denmark. ; Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark. ; Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany. ; Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, 69120 Heidelberg, Germany. ; Bejing Genomics Institute (BGI)-Shenzhen, 518083 Shenzhen, China. ; Research Centre for Prevention and Health, Capital Region of Denmark, 2600 Glostrup, Denmark. ; Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, 2600 Copenhagen, Denmark. ; Faculty of Medicine, University of Aalborg, 9100 Aalborg, Denmark. ; Novo Nordisk Foundation Center for Protein Research, Disease Systems Biology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. ; Faculty of Health Sciences, University of Southern Denmark, 5000 Odense, Denmark. ; Princess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, 80205 Jeddah, Saudi Arabia. ; Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China. ; Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong. ; Centre for Host-Microbiome Interactions, Dental Institute Central Office, Guy's Hospital, King's College London, London SE1 9RT , UK. ; Max Delbruck Centre for Molecular Medicine, 13125 Berlin, Germany. ; Department of Bioinformatics, University of Wuerzburg, 97074 Wurzburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26633628" target="_blank"〉PubMed〈/a〉
Keywords:
Biodiversity
;
Diabetes Mellitus, Type 2/drug therapy/*microbiology
;
Female
;
Gastrointestinal Microbiome/*drug effects/genetics/*physiology
;
Humans
;
Hypoglycemic Agents/pharmacology/therapeutic use
;
Male
;
Metagenome/drug effects/physiology
;
Metformin/*pharmacology/therapeutic use
;
RNA, Ribosomal, 16S/genetics
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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