An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice - PubMed (original) (raw)
An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice
Na-Ri Shin et al. Gut. 2014 May.
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.
Keywords: Intestinal Bacteria; Mucins; Obesity; Pharmacotherapy.
Comment in
- The antidiabetic gutsy role of metformin uncovered?
Burcelin R. Burcelin R. Gut. 2014 May;63(5):706-7. doi: 10.1136/gutjnl-2013-305370. Epub 2013 Jul 9. Gut. 2014. PMID: 23840042 No abstract available. - Altered microbiota in microscopic colitis.
Fischer H, Holst E, Karlsson F, Benoni C, Toth E, Olesen M, Lindén M, Sjöberg K. Fischer H, et al. Gut. 2015 Jul;64(7):1185-6. doi: 10.1136/gutjnl-2014-308956. Epub 2015 Apr 3. Gut. 2015. PMID: 25841239 Free PMC article. No abstract available.
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