The role of gut microbiota in obesity, diabetes mellitus, and effect of metformin: new insights into old diseases.

There is a recent growing evidence that abnormalities in the microbiota composition can have a major role in the development of obesity and diabetes and that some actions of metformin may be mediated by gut bacteria. Several mechanisms have been found. A reduced microbial diversity is associated to inflammation, insulin-resistance, and adiposity. In particular, a rise in the Firmicutes/Bacteroidetes ratio is related to a low-grade inflammation and to an increased capability of harvesting energy from food. Interestingly, high-fat-diet favors the growth of bacteria capable of extracting more energy from food. Changes in some metabolites, such as short-chain fatty acids (SCFAs), produced by gut microbiota, and decreased amounts of the Akkermansia muciniphila are associated with the presence of type 2 diabetes. Among the mechanisms by which metformin acts on glucose metabolism and on the cardiovascular risk, some of them are due to positive effects on gut microbiota. A shift toward positive SCFAs produced by bacteria, an increase in some bacterial strains, including A. muciniphila, and some actions on bile acids mediated by microbiota have been described. All these recent advances have been reported and discussed.