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An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice
Abstract
Background: Recent evidence indicates that the composition of the gut microbiota contributes to the development of metabolic disorders by affecting the physiology and metabolism of the host. Metformin is one of the most widely prescribed type 2 diabetes (T2D) therapeutic agents. Objective: To determine whether the antidiabetic effect of metformin is related to alterations of intestinal microbial composition. Design: C57BL/6 mice, fed either a normal-chow diet or a high-fat diet (HFD), were treated with metformin for 6 weeks. The effect of metformin on the composition of the gut microbiota was assessed by analysing 16S rRNA gene sequences with 454 pyrosequencing. Adipose tissue inflammation was examined by flow cytometric analysis of the immune cells present in visceral adipose tissue (VAT). Results: Metformin treatment significantly improved the glycaemic profile of HFD-fed mice. HFD-fed mice treated with metformin showed a higher abundance of the mucin-degrading bacterium Akkermansia than HFD-fed control mice. In addition, the number of mucin-producing goblet cells was significantly increased by metformin treatment (p<0.0001). Oral administration of Akkermansia muciniphila to HFD-fed mice without metformin significantly enhanced glucose tolerance and attenuated adipose tissue inflammation by inducing Foxp3 regulatory T cells (Tregs) in the VAT. Conclusions: Modulation of the gut microbiota (by an increase in the Akkermansia spp. population) may contribute to the antidiabetic effects of metformin, thereby providing a new mechanism for the therapeutic effect of metformin in patients with T2D. This suggests that pharmacological manipulation of the gut microbiota in favour of Akkermansia may be a potential treatment for T2D.
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In the citing paper
“Researchers have confirmed that a polyphenol-rich cranberry extract and metformin attenuate diet-induced metabolic syndrome in mice in a gut microbiota-dependent manner (16, 17).”
In the citing paper
“the administration of live (but not heat-killed) A. muciniphila was sufficient to reduce host adiposity, inflammatory markers, and insulin resistance in diet-induced obese mice97, 101.”
From The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism (2016) · cites this paper as [101]
In the citing paper
“Furthermore, delayed age-associated microbiota changes in mice have been observed by BCAA consumption, displaying a greater abundance of Bifidobacterium and Akkermansia [210], which improve glucose homeostasis and insulin sensitivity [182,211,212].”
From Impact of Protein Intake in Older Adults with Sarcopenia and Obesity: A Gut Microbiota Perspective (2020) · cites this paper as [212]
In the citing paper
“In mice fed a high-fat diet, A muciniphila given by daily oral gavage reverses fat mass gain, adipose tissue inflammation, and insulin resistance, 21,24”
From Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe −/− Mice (2016) · cites this paper as [24]
In the citing paper
“suggesting a beneficial effect in combating obesity-related metabolic disorders.”
From Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe −/− Mice (2016) · cites this paper as [24]
In the citing paper
“Furthermore, the metabolic benefits of dietary polyphenol, cranberry extract, and metformin are associated with increased amount of this bacterial species in the gut.”
From Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe −/− Mice (2016) · cites this paper as [24]
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Metadata
- Authors
- Shin, N.-R., Lee, J.-C., Lee, H.-Y., Kim, M.-S., Whon, T. W., Lee, M.-S., & Bae, J.-W.
- Affiliations
- Kyung Hee University (KR)
- Samsung Medical Center (KR)
- Corresponding author
- Bae, Jin-Woo
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2013-06-26
- Volume
- 63
- Issue
- 5
- Pages
- 727-735
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2139334262
- Cited by
- 1,550
- References
- 55
- Citations by year
- 2026: 70 · 2025: 101 · 2024: 151 · 2023: 127 · 2022: 167 · 2021: 176 · 2020: 168 · 2019: 143 · 2018: 117 · 2017: 119 · 2016: 95 · 2015: 68 · 2014: 42 · 2013: 4
- FWCI
- 31.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- Akkermansia, Akkermansia muciniphila, metformin, gut microbiota, type 2 diabetes, diet-induced obesity, high-fat diet, glucose homeostasis, glucose tolerance, mucin-degrading bacteria, goblet cells, adipose tissue inflammation, Foxp3+ regulatory T cells, visceral adipose tissue, antidiabetic mechanism
- MeSH terms
- Animals, Blood Glucose, Drug Administration Schedule, Flow Cytometry, Homeostasis, Hypoglycemic Agents, Inflammation, Intestines, Metformin, Mice, Inbred C57BL, Mice, Obese, Biomarkers, Intra-Abdominal Fat, Mice, Diet, High-Fat, Verrucomicrobia, Microbiota
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