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

Artikel i vetenskaplig tidskrift
Författare Hao Wu
E. Esteve
Valentina Tremaroli
Muhammad Tanweer Khan
Robert Caesar
Louise Mannerås Holm
Marcus Ståhlman
Lisa M. Olsson
M. Serino
M. Planas-Felix
G. Xifra
J. M. Mercader
D. Torrents
R. Burcelin
W. Ricart
Rosie Perkins
J. M. Fernandez-Real
Fredrik Bäckhed
Publicerad i Nature Medicine
Volym 23
Nummer/häfte 7
Sidor 850-+
ISSN 1078-8956
Publiceringsår 2017
Publicerad vid Wallenberglaboratoriet
Institutionen för medicin, avdelningen för molekylär och klinisk medicin
Sidor 850-+
Språk en
Länkar doi.org/10.1038/nm.4345
Ämnesord diet-induced obesity, hepatic glucose-production, chain fatty-acids, germ-free mice, akkermansia-muciniphila, gastrointestinal-tract, metabolic syndrome, gluconeogenesis, homeostasis, bacterial, Biochemistry & Molecular Biology, Cell Biology, Research & Experimental, Medicine
Ämneskategorier Klinisk medicin

Sammanfattning

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.

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