Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug.

二甲双胍通过改变原发性2型糖尿病患者的肠道微生物组以达到治疗效果

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.

二甲双胍广泛用于治疗2型糖尿病（T2D），但其作用机制尚不明确。最近的证据表明肠道微生物群是二甲双胍作用的部位。在一项双盲研究中，我们将未接受治疗的T2D患者随机分配至安慰剂或二甲双胍，经4个月治疗，显示二甲双胍对肠道微生物组具有强烈影响。这些结果在安慰剂组的一个子集中得到验证，该组在试验开始后6个月转为二甲双胍治疗。

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.