If drugs with metabolic action affect the intestinal microbiota. Literature review

Abstract

The article presents the results of studies on humans showing the association between the use of specific drugs and changes in the microbial composition of the intestinal microbiome and its functional profile. It was found that the intestinal microbe directly or indirectly affects metabolism and effectiveness of a large number of drugs, causing variability in their activation, inactivation and toxicity. On the other hand, more than 800 non‑antibiotic drugs have also been shown to have significant effects on dozens of major species of bacteria that colonize the gastrointestinal tract. It is also noted that regardless of the route of administration, some drugs will spend considerable time in the intestine and contact the microbiome (parenterally administered drugs and their metabolites may enter the intestine through bile secretion), so the intestine is an important participant in drug metabolism. Data on the main taxonomic changes of PPI users are presented and it is shown that their severity was associated with higher doses of PPIs and that such changes in the microbiome may potentiate the development of diseases, as they are similar to those that reduce colonization resistance and intestinal infections. Much attention is paid to the presence of the association of intestinal microbiome — sugar‑lowering drugs. The data on the role of the intestinal microbiome as the main target of metformin are presented. In addition, metformin has been shown to increase Akkermansia muciniphila, which is known to be correlated with obesity, type 2 diabetes mellitus, cardiovascular diseases, and inflammation, and to increase lactobacilli in the upper small intestine, which will undoubtedly contribute to its antidiabetic effect. Metformin has been shown to regulate numerous metabolic pathways by interacting with the intestinal microbiota and partially eliminate dysbacteriosis caused by type 2 diabetes, and changes in the population of microorganisms that multiply with metformin are closely related to its efficacy and tolerability. With regard to other antidiabetic drugs (glitazones, alpha‑glucosidase inhibitors, DPP‑4 inhibitors, glucagon‑like peptide‑1 receptor agonists), it has also been shown that one of their main effects is the elimination of dysbacteriosis by including bacterial nutrient changes. and the length of stay of carbohydrates in the intestine, which also emphasizes their relationship with the intestinal microbiome. It is also noted that lactobacilli have inhibitory activity against DPP‑4 inhibitors. In this aspect, measures aimed at modifying the microbiome and especially probiotics, prebiotics and antibiotics may be of particular interest, as their use can significantly change the pharmacokinetics of drugs. It is noteworthy that the pattern of intestinal microbiome observed during treatment with liraglutide is the complete opposite of what is characteristic of the metabolic syndrome. The article shows that statin intake is also associated with changes in the intestinal microbiome and hypothesizes that the response of low‑density lipoprotein cholesterol to statins may be due to the activity of bacteria containing bile hydrolases. It is also noted that the intestinal microbiota can have a significant effect on the metabolism of psychoactive drugs by modulating intestinal permeability with subsequent effects on their absorption, and on the other hand taking this group of drugs leads to significant changes in intestinal microbiome. As a result, it is concluded that today it is very important and promising to study the interaction of intestinal microbiome and the most widely used drugs for the application of methods of modulation of intestinal microbiome to optimize the effectiveness of treatment of many diseases.