Bidirectional interactions of gut microbiome and medicinal products

Abstract

In recent years, a new area of pharmacogenomics called «pharmacomicrobiomics», is being intensively developed. Its main purpose is to study the interaction of gut microbiome (GM) and various medications. One of the very important recent discoveries was that not only antibiotics, but also many commonly used drugs that do not have antibacterial properties, for example, metformin and proton pump inhibitors (PPIs), significantly change the GM composition and function. The most commonly associated GM drugs, in addition to PPI and metformin, include lipid‑lowering drugs (statins), laxatives, beta‑blockers, ACE inhibitors, and antidepressants (selective serotonin reuptake inhibitors). Changes in GM can both affect the patient’s state of health and reduce the drug effectiveness. The interactions between the intestinal microbiome and drugs are bi‑directional. On the one hand, medicines themselves can affect the composition of GM, at least in two ways. The first way is that drugs can drives into the gut microbiome from other parts of the body, what we interpret as intestinal dysbiosis. The second way, which may be dominant, is that drugs can alter the intestinal microenvironment and directly affect bacterial growth. On the other hand, more and more data are accumulating that GM itself can directly affect a person’s reaction on a particular drug by enzymatically transforming its structure and changing bioavailability, biological activity or toxicity, on which the therapeutic response depends. In particular, recent evidence suggests that GM can indirectly affect a person’s response to immunotherapy for cancer by affecting the general condition of the host and his/her immune status. Modification of GM by changing the diet, taking probiotics, or performing fecal transplantation can potentially increase the effectiveness of anti‑cancer and other treatments.