Disease and Health Research: New Insights Vol. 5

Abstract

Abstract: The present study discusses the role of microbiota in the metabolism of psychotropic drugs as well as the dysbiosis associated with the antimicrobial properties of these agents. Psychotropic drugs are endowed with antimicrobial properties and are known to alter the gut microbiome, selectively depleting the Bacteroidetes phylum, and leading to obesity.

It is well-established that obesity has reached epidemic proportions throughout the world, however, it is less known that its rates are two to three times higher in mentally ill patients compared to the general population. Both psychotropic drugs-induced dysmetabolism and high fat diet-related weight gain present with a common enteric microbial pattern, and depletion of the Bacteroidetes phylum, suggesting an overlapping pathology. Others have opined that the loss of Bacteroidetes-generated metabolites is the common denominator of weight gain induced either by an unhealthy diet or psychotropic drugs.

Since germ-free animals exposed to psychotropics have not demonstrated weight gain, altered commensal flora composition is believed to be necessary and sufficient to induce dysmetabolism. Conversely, not only do psychotropics disrupt the composition of gut microbiota but the latter alter the metabolism of the former. For example, drug metabolism starts in the gut, rather than the liver as it was construed in the past.

The potential biomarkers reflecting the status of the Bacteroidetes phylum have been discussed and a closer look at nutritional interventions, fecal microbiota transplantation, and transcranial magnetic stimulation strategies has been taken that may lower obesity rates in chronic psychiatric patients. Obesity is a modifiable risk factor of general morbidity, therefore restoring the physiological levels of Bacteroidetes phylum by various strategies may attenuate or reverse the excess weight in chronic psychiatric patients. If validated, the biological markers described here may offer the clinician additional feedback to estimate the imminence of weight-related complications.

Psychotropic drugs deplete the intestinal Bacteroidetes phylum. The absence of metabolites generated by these microbes may under-activate xenobiotic sensors aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR), disrupting the transcription of genes related to psychotropic drug metabolism, lipid, and redox homeostasis, leading to altered bioavailability of antipsychotic agents, weight gain, and lowered body iron stores.