Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug
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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A study of metformin suggested that a shift in microbial community structure contributed in part to its beneficial metabolic effects.
“And in a recent elegant study with metformin, a shift in microbial community structure was suggested to contribute in part to its observed beneficial metabolic effects60.”
From Development of a gut microbe–targeted nonlethal therapeutic to inhibit thrombosis potential (2018) · cites this paper as [60]
Some anti-diabetic effects of metformin therapy appear to be mediated by alterations in gut microbiota composition, as microbial transplantation transmits anti-diabetic effects to germ-free mice from metformin-treated donors.
“Recent studies by Bäckhed and colleagues show that some of the anti-diabetic effects of metformin therapy appear to be mediated by alterations in gut microbiota composition, since microbial transplantation studies reveal transmission of anti-diabetic effects in recipient germ free mice following fecal transfer from metformin treated donors160.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [160]
Studies comparing T2D individuals treated or not with metformin identified a higher level of E. coli and a lower level of Intestinibacter in metformin-treated individuals, and reduced levels of butyrate-producing bacteria in untreated individuals compared to healthy controls.
“Studies comparing individuals with T2D treated or not with metformin identified a higher level of E. coli and a lower level of Intestinibacter in the metformin-treated individuals, while confirming reduced levels of butyrate-producing bacteria such as Roseburia spp., F. prausnitzii, and unnamed Clostridiales in the untreated individuals compared to healthy controls5, 6, 34, 35.”
From The gut microbiome in atherosclerotic cardiovascular disease (2017) · cites this paper as [35]
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- Authors
- 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.
- Affiliations
- University of Gothenburg (SE)
- Universitat de Girona (ES)
- Barcelona Supercomputing Center (ES)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Université Toulouse III - Paul Sabatier (FR)
- University of Copenhagen (DK)
- Corresponding author
- Bäckhed, Fredrik
- ORCID
- Venue
- Nature Medicine
- Published
- 2017-05-22
- Volume
- 23
- Issue
- 7
- Pages
- 850-858
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2617940752
- Cited by
- 1,632
- References
- 74
- Citations by year
- 2026: 127 · 2025: 144 · 2024: 219 · 2023: 172 · 2022: 224 · 2021: 217 · 2020: 200 · 2019: 171 · 2018: 118 · 2017: 37
- FWCI
- 58.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- HAL (submittedVersion)
- Funders
- Helsingin Yliopisto
- Novo Nordisk Fonden (NNF13OC0008163, NNF15OC0016798)
- Wageningen University and Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- metformin, type 2 diabetes, gut microbiota, mechanism of action, glucose tolerance, fecal microbiota transplantation, germ-free mice, metalloproteins, metal transporters
- MeSH terms
- Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Animals, Bile Acids and Salts, Diabetes Mellitus, Type 2, DNA, Bacterial, Double-Blind Method, Fatty Acids, Volatile, Feces, Female, Germ-Free Life, Glucose Tolerance Test, Humans, Hypoglycemic Agents, Male, Metformin, Middle Aged, Mice, Metagenomics, In Vitro Techniques
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