Clinical significance of microbiota changes under the influence of psychotropic drugs. An updated narrative review

Abstract

Relationship between drugs and microbiota is bilateral. Proper composition thus function of microbiota is a key to some medications used in modern medicine. However, there is also the other side of the coin. Pharmacotherapeutic agents can modify the microbiota significantly, which consequently affects its function. A recently published study showed that nearly 25% of drugs administered to humans have antimicrobial effects. Multiple antidepressants are antimicrobials,. and antibiotics with proven antidepressant effects do exist. On the other hand, antibiotics (e.g., isoniaside, minocycline) confer mental phenotype changes, and adverse effects caused by some antibiotics include neurological and psychological symptoms which further supports the hypothesis that intestinal microbiota may affect the function of the central nervous system. Here we gathered comprehensively data on drugs used in psychiatry regarding their antimicrobial properties. We believe our data has strong implications for the treatment of psychiatric entities. Nevertheless the study of ours highlights the need for more well-designed trials aimed at analysis of gut microbiota function.

Keywords: brain; gut; microbiota; pharmacomicrobiomics; psychotropic drugs.

Figure 1

Microbiota interaction with drugs. Based on Tuteja and Ferguson (2019). Metabolic activity of microbiota towards xenobiotics may be direct (e.g., acetylation, denitration, hydrolysis, etc.), which may consistently make a given therapeutic effective or lose its efficacy completely. Indirectly, the metabolites of the intestinal microbiota may compete with drugs for enzymes or receptors, which potentially modulate therapeutic efficacy, also in the mechanisms of altered expression of selected genes involved in intracellular signaling. Parallelly, certain drugs might change the gut environment and promote/inhibit certain bugs bloom which in turn may impact the pharmacokinetics of taken drugs.

Figure 2

The impact of certain factors on one’s behavior. A variety of factors influence one’s behavior. Apart from a genetic factors, multiple environmental ones, including microbiota along with its metabolites, have the potential to affect behavior.

Figure 3

Vulnerability-stress model. This is a model illustrating a psychological theory about the relationship between internal factors, psychosocial factors and vulnerability to stress, which is associated with an increased risk of various diseases, including mental theses. The composition of the gut microbiota appears to be an important internal factor that, through appropriate modulation, can increase individual resistance to stress. Disturbances in the composition of the gut microbiota, are responsible for a number of reactions of the body exposed to stress. Among other things, the gut microbiota influences the concentration of cortisol in the blood. In addition, it participates in the coordination of biochemical reactions in metabolic pathways. These pathways are either stimulated or inhibited, depending on changes in the quantity and quality of the bacterial enterotype. Also, this mechanism at least partially explains the body’s various responses to stress.

Figure 4

Microbiotic and cardiometabolic effects of second-generation antipsychotics. Schematic presentation of possible mechanisms responsible for metabolic disorders secondary to SGA treatment. Based on Skonieczna-Żydecka et al. (2019) and Singh et al. (2022). Metabolic disturbances observed in the course of antipsychotics administration may be caused by adverse changes in the composition of gut microbiome - changes in the abundance of major types of gut microbes which consequently disturb gut barrier integrity and SCFAs pool. This might phenotypically manifests as weight gain, hypertriglyceridemia, hypercholesterolemia, hypertension and impaired glucose metabolism and the mechanisms involved include lowering basal metabolic rate, enhancement of lipogenic enzymes expression and releasing of free fatty acids.

Figure 5

The influence of microbiota on the effectiveness of treatment in psychiatry. A mentally ill patient has a specific composition of intestinal microbiota. This composition differs from that of the intestinal microbiota of the healthy population. Psychopharmacotherapy, for example, with antipsychotic drugs, which, in addition to the known mechanism of action, that is, among other things, blockade of dopamine D2 receptors, also has a bactericidal effect by changing the composition of the intestinal microbiota of the patient. The alleviation of clinical symptoms of mental illness may depend not only on the known pharmacological effects of psychotropic drugs, but also on little-known interactions of these drugs with the intestinal microbiota. These interactions may also have another face. With long-term treatment, metabolic disorders resulting from the administration of antipsychotic drugs are observed, which may be related to microbiota disorders. Severe metabolic disorders are one of the most common reasons for discontinuing psychopharmacological treatment or forcing doctors to change the drug, despite its good effect on the symptoms of the psychiatric disorder. Supplementation with appropriate probiotic strains, especially those that affect the brain-gut axis, can significantly alleviate the discomfort associated with metabolic disorders and at the same time support the positive effects of the drug on the patient.