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Nat Med. 2017 Jul;23(7):850-858. doi: 10.1038/nm.4345. Epub 2017 May 22.

Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug.

Author information

1
Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
2
Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona, Hospital Josep Trueta, Girona, Spain.
3
Departament de Medicina, Facultat de Medicina, University of Girona, Girona, Spain.
4
Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
5
IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France.
6
Barcelona Supercomputing Center (BSC), Joint BSC-CRG-IRB Research Program in Computational Biology, Barcelona, Spain.
7
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
8
Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France.
9
Université Paul Sabatier (UPS), Unité Mixte de Recherche 1048, Institut de Maladies Métaboliques et Cardiovasculaires, Toulouse, France.
10
Sahlgrenska University Hospital, Gothenburg, Sweden.
11
Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.

Abstract

Metformin is widely used in the treatment of type 2 diabetes (T2D), but its mechanism of action is poorly defined. Recent evidence implicates the gut microbiota as a site of metformin action. In a double-blind study, we randomized individuals with treatment-naive T2D to placebo or metformin for 4 months and showed that metformin had strong effects on the gut microbiome. These results were verified in a subset of the placebo group that switched to metformin 6 months after the start of the trial. Transfer of fecal samples (obtained before and 4 months after treatment) from metformin-treated donors to germ-free mice showed that glucose tolerance was improved in mice that received metformin-altered microbiota. By directly investigating metformin-microbiota interactions in a gut simulator, we showed that metformin affected pathways with common biological functions in species from two different phyla, and many of the metformin-regulated genes in these species encoded metalloproteins or metal transporters. Our findings provide support for the notion that altered gut microbiota mediates some of metformin's antidiabetic effects.

PMID:
28530702
DOI:
10.1038/nm.4345
[Indexed for MEDLINE]

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