Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug
Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug
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DOI：
10.1038/nm.4345
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发表时间：
2017-07-01
期刊：
影响因子：
82.9
通讯作者：
Backhed, Fredrik
中科院分区：
文献类型：
--
作者：
Wu, Hao;Esteve, Eduardo;Backhed, Fredrik
二甲双胍广泛用于治疗2型糖尿病（T2D），但其作用机制尚不清楚。最近的证据表明肠道微生物群是二甲双胍的作用部位。在一项双盲研究中，我们将未经治疗的T2D患者随机分配至安慰剂或二甲双胍治疗4个月，结果表明二甲双胍对肠道微生物组有很强的影响。这些结果在试验开始后6个月转换为二甲双胍的安慰剂组亚组中得到验证。从二甲双胍治疗的供体转移粪便样本（治疗前和治疗后4个月获得）到无菌小鼠显示，接受二甲双胍改变的微生物群的小鼠的葡萄糖耐量得到改善。通过在肠道模拟器中直接研究二甲双胍-微生物群相互作用，我们发现二甲双胍影响了两个不同门物种中具有共同生物学功能的途径，并且这些物种中的许多二甲双胍调节基因编码金属蛋白或金属转运蛋白。我们的研究结果为改变肠道微生物群介导二甲双胍的一些抗糖尿病作用的观点提供了支持。
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.