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二甲双胍:老朋友,新作用途径——肠道微生物组的影响?

Metformin: old friend, new ways of action-implication of the gut microbiome?

机构信息

Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.

出版信息

Curr Opin Clin Nutr Metab Care. 2018 Jul;21(4):294-301. doi: 10.1097/MCO.0000000000000468.

Abstract

PURPOSE OF REVIEW

Gut dysbiosis was recently associated with the occurrence of type 2 diabetes (T2D). In addition to this finding, an increasing number of studies performed upon the last 5 years have also shown that metformin treatment leads to changes in gut bacterial composition in diabetic patients. This review focuses on the articles describing the effects of metformin on gut homeostasis (including the gut microbiota) and proposes potential mechanisms involved in those effects.

RECENT FINDINGS

Several human and animal studies emphasized that metformin alters the gut microbiota composition by enhancing the growth of some bacteria, such as Akkermansia muciniphila, Escherichia spp. or Lactobacillus and by decreasing the levels of some other ones like Intestinibacter. In-vitro studies also demonstrated a direct action of metformin on the growth of A. muciniphila and Bifidobacterium adolescentis. Moreover, in the intestines, metformin does not only improve the glucose uptake, but it also promotes the short-chain fatty acid (SCFA) production, protects the intestinal barrier and regulates the secretion of gut peptides SUMMARY: It is now clear that gut microbiota participates to the glucose-lowering effects of metformin in the context of diabetes. Further work is now needed to determine the exact mechanisms of action of the drug and to understand by which processes metformin is able to enhance the growth of some bacteria exhibiting beneficial effects for the host.

摘要

目的综述

肠道菌群失调最近与 2 型糖尿病(T2D)的发生有关。除了这一发现,在过去的 5 年中进行的越来越多的研究还表明,二甲双胍治疗会导致糖尿病患者肠道细菌组成发生变化。这篇综述重点介绍了描述二甲双胍对肠道稳态(包括肠道微生物群)影响的文章,并提出了这些影响所涉及的潜在机制。

最近的发现

几项人体和动物研究强调,二甲双胍通过增强 Akkermansia muciniphila、Escherichia spp. 或 Lactobacillus 等某些细菌的生长,同时降低 Intestinibacter 等其他一些细菌的水平,从而改变肠道微生物群的组成。体外研究还表明,二甲双胍对 A. muciniphila 和 Bifidobacterium adolescentis 的生长有直接作用。此外,在肠道中,二甲双胍不仅改善葡萄糖摄取,还促进短链脂肪酸(SCFA)的产生,保护肠道屏障并调节肠道肽的分泌。

总结

现在很清楚,肠道微生物群参与了糖尿病患者二甲双胍的降血糖作用。现在需要进一步的工作来确定药物的确切作用机制,并了解二甲双胍通过哪些过程能够增强某些具有宿主有益影响的细菌的生长。

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