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

Hao Wu; Eduardo Esteve; Valentina Tremaroli; Muhammad Tanweer Khan; Robert Caesar; Louise Mannerås-Holm; Marcus Ståhlman; Lisa M Olsson; Matteo Serino; Mercè Planas-Fèlix; Gemma Xifra; Josep M Mercader; David Torrents; Rémy Burcelin; Wifredo Ricart; Rosie Perkins; José Manuel Fernàndez-Real; Fredrik Bäckhed

doi:10.1038/nm.4345

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

Hao Wu, Eduardo Esteve, Valentina Tremaroli, Muhammad Tanweer Khan, Robert Caesar, Louise Mannerås-Holm, Marcus Ståhlman, Lisa M Olsson, Matteo Serino, Mercè Planas-Fèlix, Gemma Xifra, Josep M Mercader, David Torrents, Rémy Burcelin, Wifredo Ricart, Rosie Perkins, José Manuel Fernàndez-Real, Fredrik Bäckhed

535 Citations (Scopus)

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.

Original language	English
Journal	Nature Medicine
Volume	23
Issue number	7
Pages (from-to)	850-858
Number of pages	9
ISSN	1078-8956
DOIs	https://doi.org/10.1038/nm.4345
Publication status	Published - 1 Jul 2017

Keywords

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/nm.4345

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Wu, H., Esteve, E., Tremaroli, V., Khan, M. T., Caesar, R., Mannerås-Holm, L., Ståhlman, M., Olsson, L. M., Serino, M., Planas-Fèlix, M., Xifra, G., Mercader, J. M., Torrents, D., Burcelin, R., Ricart, W., Perkins, R., Fernàndez-Real, J. M., & Bäckhed, F. (2017). Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nature Medicine, 23(7), 850-858. https://doi.org/10.1038/nm.4345

Wu, H, Esteve, E, Tremaroli, V, Khan, MT, Caesar, R, Mannerås-Holm, L, Ståhlman, M, Olsson, LM, Serino, M, Planas-Fèlix, M, Xifra, G, Mercader, JM, Torrents, D, Burcelin, R, Ricart, W, Perkins, R, Fernàndez-Real, JM & Bäckhed, F 2017, 'Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug', Nature Medicine, vol. 23, no. 7, pp. 850-858. https://doi.org/10.1038/nm.4345

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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.",

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AU - Caesar, Robert

AU - Mannerås-Holm, Louise

AU - Ståhlman, Marcus

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AU - Serino, Matteo

AU - Planas-Fèlix, Mercè

AU - Xifra, Gemma

AU - Mercader, Josep M

AU - Torrents, David

AU - Burcelin, Rémy

AU - Ricart, Wifredo

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AU - Fernàndez-Real, José Manuel

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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

Abstract

Keywords

UN SDGs

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