Decoding psychotropic-induced metabolic disturbances: gut-brain axis, multi-omics, and nutrition-lifestyle integration

Psychotropic medications remain central to psychiatric treatment, yet their use is frequently accompanied by a substantial metabolic burden. Metabolic adverse effects, including weight gain, insulin resistance, dysglycemia, dyslipidemia, and hypertension, complicated clinical management and undermine long-term adherence. Although evidence-based monitoring and mitigation approaches exist, the molecular determinants of individual susceptibility and the drivers of interindividual variability in metabolic outcomes remain insufficiently defined. Emerging evidence identifies the gut-brain-metabolic axis as a key mechanistic interface, with psychotropic medications altering gut microbiota and associated metabolic pathways that contribute to metabolic complications. Multi-omics strategies are beginning to illuminate the complex molecular networks underlying these adverse effects; however, most findings still arise from isolated omics layers, limiting mechanistic resolution and translational utility. Integrative analytical frameworks, including artificial intelligence, now enable the synthesis of molecular, clinical, environmental, lifestyle, and dietary factors to support more precise and individualized intervention. In this narrative review, we synthesize current clinical and mechanistic advances in understanding psychotropic-induced metabolic dysfunction, with a focus on insulin resistance and the gut-brain-metabolic axis and highlight how multi-omics, environmental factors and computational strategies may advance future precision approaches in psychiatric care.