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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

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 mo... Full description

Journal Title: Nature Medicine 2017-07, Vol.23 (7), p.850-858
Main Author: Wu, Hao
Other Authors: Esteve, Eduardo , Tremaroli, Valentina , Khan, Muhammad Tanweer , Caesar, Robert , Mannerås-Holm, Louise , Ståhlman, Marcus , Olsson, Lisa M , Serino, Matteo , Planas-Fèlix, Mercè , Xifra, Gemma , Mercader, Josep M , Torrents, David , Burcelin, Rémy , Ricart, Wifredo , Perkins, Rosie , Fernàndez-Real, José Manuel , Bäckhed, Fredrik
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: United States: Nature Publishing Group
ID: ISSN: 1078-8956
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title: Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug
format: Article
creator:
  • Wu, Hao
  • Esteve, Eduardo
  • Tremaroli, Valentina
  • Khan, Muhammad Tanweer
  • Caesar, Robert
  • Mannerås-Holm, Louise
  • Ståhlman, Marcus
  • Olsson, Lisa M
  • Serino, Matteo
  • Planas-Fèlix, Mercè
  • Xifra, Gemma
  • Mercader, Josep M
  • Torrents, David
  • Burcelin, Rémy
  • Ricart, Wifredo
  • Perkins, Rosie
  • Fernàndez-Real, José Manuel
  • Bäckhed, Fredrik
subjects:
  • akkermansia-muciniphila
  • Analysis
  • Animals
  • bacterial
  • Bile Acids and Salts - metabolism
  • Biochemistry & Molecular Biology
  • Care and treatment
  • Cell Biology
  • chain fatty-acids
  • Clinical Medicine
  • Coding
  • Dextrose
  • Diabetes
  • Diabetes mellitus
  • Diabetes Mellitus, Type 2 - drug therapy
  • Diabetes Mellitus, Type 2 - microbiology
  • diabète de type 2
  • diet-induced obesity
  • digestive
  • digestive system
  • Digestive tract
  • DNA, Bacterial - analysis
  • Dosage and administration
  • Double-Blind Method
  • Drug therapy
  • endocrine system diseases
  • Fatty Acids, Volatile - metabolism
  • Fecal Microbiota Transplantation
  • Feces - chemistry
  • Feces - microbiology
  • Female
  • Gastroenterology
  • Gastrointestinal Microbiome - genetics
  • gastrointestinal-tract
  • Germ-Free Life
  • germ-free mice
  • Germfree
  • gluconeogenesis
  • Glucose
  • Glucose tolerance
  • Glucose Tolerance Test
  • Health aspects
  • hepatic glucose-production
  • homeostasis
  • Human health
  • Human health and pathology
  • Humans
  • Hypoglycemic Agents - therapeutic use
  • Hépatology
  • Hépatology and Gastroenterology
  • In Vitro Techniques
  • Intestinal microflora
  • Klinisk medicin
  • Life Sciences
  • Male
  • Medicine
  • metabolic diseases
  • metabolic syndrome
  • Metagenomics
  • Metformin
  • Metformin - therapeutic use
  • metformine
  • Mice
  • microbiome
  • Microbiota (Symbiotic organisms)
  • microbiote digestif
  • Middle Aged
  • nutritional
  • oral
  • pathology
  • Pathways
  • Research & Experimental
  • Rodents
  • skin physiology
  • Type 2 diabetes
  • type ii diabetes
ispartof: Nature Medicine, 2017-07, Vol.23 (7), p.850-858
description: 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.
language: eng
source:
identifier: ISSN: 1078-8956
fulltext: no_fulltext
issn:
  • 1078-8956
  • 1546-170X
  • 1744-7933
url: Link


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titleMetformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug
creatorWu, Hao ; Esteve, Eduardo ; Tremaroli, Valentina ; Khan, Muhammad Tanweer ; Caesar, Robert ; Mannerås-Holm, Louise ; Ståhlman, Marcus ; Olsson, Lisa M ; Serino, Matteo ; Planas-Fèlix, Mercè ; Xifra, Gemma ; Mercader, Josep M ; Torrents, David ; Burcelin, Rémy ; Ricart, Wifredo ; Perkins, Rosie ; Fernàndez-Real, José Manuel ; Bäckhed, Fredrik
creatorcontribWu, Hao ; Esteve, Eduardo ; Tremaroli, Valentina ; Khan, Muhammad Tanweer ; Caesar, Robert ; Mannerås-Holm, Louise ; Ståhlman, Marcus ; Olsson, Lisa M ; Serino, Matteo ; Planas-Fèlix, Mercè ; Xifra, Gemma ; Mercader, Josep M ; Torrents, David ; Burcelin, Rémy ; Ricart, Wifredo ; Perkins, Rosie ; Fernàndez-Real, José Manuel ; Bäckhed, Fredrik ; Wallenberg Laboratory ; Institute of Medicine, Department of Molecular and Clinical Medicine ; Göteborgs universitet ; Gothenburg University ; Sahlgrenska Academy ; Sahlgrenska akademin ; Wallenberglaboratoriet ; Institutionen för medicin, avdelningen för molekylär och klinisk medicin
descriptionMetformin 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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languageeng
publisherUnited States: Nature Publishing Group
subjectakkermansia-muciniphila ; Analysis ; Animals ; bacterial ; Bile Acids and Salts - metabolism ; Biochemistry & Molecular Biology ; Care and treatment ; Cell Biology ; chain fatty-acids ; Clinical Medicine ; Coding ; Dextrose ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - microbiology ; diabète de type 2 ; diet-induced obesity ; digestive ; digestive system ; Digestive tract ; DNA, Bacterial - analysis ; Dosage and administration ; Double-Blind Method ; Drug therapy ; endocrine system diseases ; Fatty Acids, Volatile - metabolism ; Fecal Microbiota Transplantation ; Feces - chemistry ; Feces - microbiology ; Female ; Gastroenterology ; Gastrointestinal Microbiome - genetics ; gastrointestinal-tract ; Germ-Free Life ; germ-free mice ; Germfree ; gluconeogenesis ; Glucose ; Glucose tolerance ; Glucose Tolerance Test ; Health aspects ; hepatic glucose-production ; homeostasis ; Human health ; Human health and pathology ; Humans ; Hypoglycemic Agents - therapeutic use ; Hépatology ; Hépatology and Gastroenterology ; In Vitro Techniques ; Intestinal microflora ; Klinisk medicin ; Life Sciences ; Male ; Medicine ; metabolic diseases ; metabolic syndrome ; Metagenomics ; Metformin ; Metformin - therapeutic use ; metformine ; Mice ; microbiome ; Microbiota (Symbiotic organisms) ; microbiote digestif ; Middle Aged ; nutritional ; oral ; pathology ; Pathways ; Research & Experimental ; Rodents ; skin physiology ; Type 2 diabetes ; type ii diabetes
ispartofNature Medicine, 2017-07, Vol.23 (7), p.850-858
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21Gothenburg University
22Sahlgrenska Academy
23Sahlgrenska akademin
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25Institutionen för medicin, avdelningen för molekylär och klinisk medicin
title
0Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug
1Nature Medicine
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descriptionMetformin 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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11Dextrose
12Diabetes
13Diabetes mellitus
14Diabetes Mellitus, Type 2 - drug therapy
15Diabetes Mellitus, Type 2 - microbiology
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titleMetformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug
authorWu, Hao ; Esteve, Eduardo ; Tremaroli, Valentina ; Khan, Muhammad Tanweer ; Caesar, Robert ; Mannerås-Holm, Louise ; Ståhlman, Marcus ; Olsson, Lisa M ; Serino, Matteo ; Planas-Fèlix, Mercè ; Xifra, Gemma ; Mercader, Josep M ; Torrents, David ; Burcelin, Rémy ; Ricart, Wifredo ; Perkins, Rosie ; Fernàndez-Real, José Manuel ; Bäckhed, Fredrik
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72Rodents
73skin physiology
74Type 2 diabetes
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abstractMetformin 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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doi10.1038/nm.4345
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