The Microbiota-Gut-Brain Axis: A New Frontier in Precision Neuropsychopharmacology

Introduction: The gut microbiota has emerged as a relevant modulator of brain function, behavior, and treatment response through the microbiota-gut-brain axis. This bidirectional system may influence the pharmacokinetics and pharmacodynamics of psychotropic drugs, offering new perspectives for neuropsychopharmacology and precision psychiatry. The aim of this review was to synthesize current evidence on the mechanisms by which gut microbiota affects the absorption, metabolism, efficacy, and safety of neuroactive drugs, and to explore its clinical implications in psychiatric practice. Methods: A narrative review was conducted using preclinical and clinical studies published in recent years. Evidence was gathered from peer-reviewed articles indexed in PubMed, Scopus, and Web of Science, integrating findings from microbiology, neuroscience, pharmacology, and psychiatry. Particular attention was given to microbiota-drug interactions involving antidepressants, antipsychotics, mood stabilizers, and anxiolytics. Results: Gut microorganisms may modulate psychotropic drug effects through enzymatic biotrans-formation, alterations in host metabolic pathways, regulation of neurotransmitter systems, and modulation of immune and endocrine signaling. Differences in microbiota composition have been associated with variability in therapeutic response, tolerability, and adverse-effect profiles. Emerging evidence also suggests that microbiota-targeted strategies, including probiotics, prebiotics, and dietary interventions, may act as adjuvant approaches to improve efficacy and reduce side effects. Discussion: Although the microbiota-gut-brain axis represents a biologically plausible and clinically relevant determinant of psychotropic outcomes, current evidence remains heterogeneous and largely associative. Methodological variability, small sample sizes, and limited longitudinal data restrict translation into routine clinical practice. Microbiota-informed prescribing appears promising, but requires standardized multi-omics profiling, harmonized sampling procedures, and robust prospective validation. Conclusion: Gut microbiota may play an important role in psychotropic drug outcomes and could support more personalized, effective, and safer psychiatric care. Further mechanistic studies and standardized clinical trials are needed before microbiota-informed prescribing can be reliably implemented.