Metformin as a drug modifyinggut microbiota
Metformin is currently the most widely used drug in patients with type 2 diabetes mellitus (DM) due to its relative safety, low cost and positive effect on glycemia and cardiovascular mortality. Nevertheless, the mechanisms of its action to date remain not fully understood. In recent years, evidence has accumulated that the antidiabetic effects of metformin can be mediated through the colon, in particular, by affecting the gut microbiota (GM). A review of the data of several studies is presented, indicating that in patients with type 2 DM, metformin administration is associated with a rapid change in the composition and functions of GM in parallel with a decrease in the level of HbA1c and the level of glycemia. GM transplantation to sterile mice demonstrated that GM modified under the influence of metformin can improve glucose metabolism.Transcriptome analysis of feces cultured in vitro with metformin showed that it has direct effects on the microbiota and regulates the expression of genes encoding metalloproteins in gut bacteria. When conducting genome-wide sequencing of fecal samples in patients with newly diagnosed type 2 DM, a sharp change in the composition of GM was revealed after 2 and 4 months of metformin treatment, in particular, a significant increase in the contents of Escherichia and Intestinibacter, as well as B. adolescenti, A. muciniphila, Butyrivibrio, Bifidobacterium bifidum and Megasphaera. Metformin is thought to interact with various gut bacteria through the regulation of metal homeostasis. However, additional studies combining metabolomics and metaproteomics are neededto identify additional microbial metabolites or proteins and to determine how they interact with the host’s targets and improve its metabolism.