Abstract

A number of human and animal studies have demonstrated that the hyperglycemia-lowering effects of metformin may result from modulation of the gut microbiota population. Metformin changes the Firmicutes/Bacteroidetes ratio and enhances the growth of some bacteria, such as Akkermansia muciniphila, Escherichia spp. or Lactobacillus and reduce the levels of others such as Intestinibacter. Moreover, in the intestine, metformin not only improves glucose absorption, but also promotes the production of short-chain fatty acids (SCFAs), regulates the secretion of the glucose-lowering hormone glucagon-like peptide 1 (GLP‑1) and other intestinal peptides, inhibits the Farnesoid-X-receptor (FXR) and resorption of the bile acid pool, and may reduce intestinal permeability barrier by increasing the expression of mucin and tight junction proteins, modulates the immune response, has an anti-inflammatory effect, etc. Thus, research results indicate that the intestinal microbiota is involved not only in the hypoglycemic effect of metformin in diabetes mellitus type 2, but also in the implementation of its numerous pleiotropic effects.

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