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

TY - JOUR

T1 - Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug

AU - Wu, Hao

AU - Esteve, Eduardo

AU - Tremaroli, Valentina

AU - Khan, Muhammad Tanweer

AU - Caesar, Robert

AU - Mannerås-Holm, Louise

AU - Ståhlman, Marcus

AU - Olsson, Lisa M

AU - Serino, Matteo

AU - Planas-Fèlix, Mercè

AU - Xifra, Gemma

AU - Mercader, Josep M

AU - Torrents, David

AU - Burcelin, Rémy

AU - Ricart, Wifredo

AU - Perkins, Rosie

AU - Fernàndez-Real, José Manuel

AU - Bäckhed, Fredrik

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1038/nm.4345

DO - 10.1038/nm.4345

M3 - Journal article

C2 - 28530702

SN - 1078-8956

VL - 23

SP - 850

EP - 858

JO - Nature Medicine

JF - Nature Medicine

IS - 7

ER -