Metformin Alters the Gut Microbiome of Individuals With Treatment-Naive Type 2 Diabetes, Contributing to the Therapeutic Effects of the Drug

Nat Med. 2017 Jul;23(7):850-858. doi: 10.1038/nm.4345. Epub 2017 May 22.

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. 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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Animals
  • Bile Acids and Salts / metabolism
  • DNA, Bacterial / analysis*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / microbiology
  • Double-Blind Method
  • Fatty Acids, Volatile / metabolism
  • Fecal Microbiota Transplantation
  • Feces / chemistry
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome / genetics*
  • Germ-Free Life
  • Glucose Tolerance Test
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • In Vitro Techniques
  • Male
  • Metagenomics
  • Metformin / therapeutic use*
  • Mice
  • Middle Aged

Substances

  • Bile Acids and Salts
  • DNA, Bacterial
  • Fatty Acids, Volatile
  • Hypoglycemic Agents
  • Metformin