Inter-individual variability in the metabolism of psychotropic drugs by the enzyme activities from the human gut microbiome

The interaction between marketed drugs and the gut microbiome is increasingly being recognized, and it is now known that enzymes produced by the bacteria in the human gut can degrade psychotropic drugs. However, the degree of inter-individual variation in their metabolism remains largely unknown. Here, we present a simple model for detecting individual drug-microbiome interaction using fecalase. We incubated fecalase prepared from freshly collected stool samples from healthy volunteers (n = 18) and incubated with nine selected psychotropic medications. We proved fecalase retained enzymatic activities and showed the degree of drug degradation differed significantly for different psychotropic drugs, and there was significant inter-individual variation in the metabolism of phenytoin, amitriptyline, and chlorpromazine with the inter-individual point difference between the strongest and weakest metabolizer of 85 %, 39 %, and 30 % respectively. These findings highlight the potential of fecalase as a model for studying personalized drug metabolism and underscore the importance of considering gut microbiome variability in pharmacological research.