Metformin, Microbiota and Health

Abstract

Microbiota and its role in the human bodyMicrobiota, whose composition and activity are associated with health and the development of diseases, 1 are composed of different microorganisms, including bacteria, bacteriophages, eukaryotic viruses, and fungi that inhabit body surfaces and cavities usually in a beneficial relationship for both parties. 2 Most microbiotás microorganisms are found in the gastrointestinal tract (mainly colon), and their composition are influenced by the type of birth, lifestyle, diet in the first years of life, medications, and host genetics. 2 Human microbiota composition comprises approximately 1,000 species, where bacteria are considered the main constituents corresponding to the five main phyla: Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, and Verrucomicrobia. 3 Studies have pointed out that the number of these microbial cells is around 1 × 10 14 against 1 × 10 13 of eukaryotic cells, thus indicating that the number of microbial cells is 10 times greater than the number of human cells. 4 Hence, the microbiota can be considered as a metabolic organ supporting important functions in the host, such as digestion and absorption of food nutrients, the regulation of the immune system, regulation of the endocrine and neurological functions, alteration of the mechanism of the action of drugs, removing toxins, and the production of various compounds, including vitamins and short chain fatty acids (SC-FAs). 2,5 The maintenance of diverse microbiota with a functionally stable microbiome contributes to the homeostasis and health of the host. 6 Modulations in the composition of the microbiota, compromising the symbiotic relationship between the host and microorganisms in a process called dysbiosis, are often associated with the development of autoimmune diseases, obesity, diabetes, cancers, neurological diseases among others. 7,8 Dysbiosis can be classified into three types: (1) loss of beneficial microorganisms, (2) an increase in opportunistic pathogens, and (3) loss of microbiota diversity; despite this categorization, the three scenarios usually occur simultaneously. 9 Thus, factors capable of promoting changes in the composition of the microbiota are considered risk factors for diseases associated with a microbial imbalance. 9 Therefore, drugs able to restore the microbiota balance have become promising candidates for the treatment of these pathologies. In this context, metformin is an important candidate, so are several factors that regulate its uptake and activity. Metformin: Brief history and the main mechanisms of actionMetformin (1,1-dimethylbiguanide) is a drug of the biguanide class derived from guanidine, the active substance in Galega officinalis. The processes for its synthesis began in 1920, from the discovery of the antidiabetic properties in 1918 of guanidine. 10 Due to its high antihyperglycemic efficiency, without causing