The gut–brain axis in pharmacology: microbiome-driven modulation of CNS drugs and neuropsychiatric outcomes

Background The gut–brain axis has emerged as a critical regulator of Central Nervous System (CNS) pharmacology, significantly influencing drug response and neuropsychiatric outcomes through complex interactions between the gut microbiota and host systems. Objective This review aims to examine the role of gut microbiota in modulating the pharmacokinetics and pharmacodynamics of CNS drugs, and to explore their implications in neuropsychiatric disorders. Key findings Accumulating evidence indicates that microbial enzymes and metabolites can alter drug absorption, metabolism, and bioavailability, particularly for antidepressants such as Selective Serotonin Reuptake Inhibitors (SSRIs) and Tricyclic Antidepressants (TCAs). In turn, psychotropic medications can modify gut microbial composition, leading to dysbiosis and variability in therapeutic outcomes. Microbiota-derived metabolites, immune signaling pathways, and host genetic factors (e.g., cytochrome P450 polymorphisms) collectively contribute to interindividual differences in drug efficacy and safety. Conclusion Integration of microbiome profiling into pharmacological research holds significant potential for advancing precision medicine in neuropsychiatry. However, challenges such as methodological heterogeneity, limited longitudinal clinical data, and lack of standardized biomarkers must be addressed to enable clinical translation.