IUPHAR Themed Review: The Gut Microbiome in Schizophrenia.

Gut microbial dysbiosis or altered gut microbial consortium, in schizophrenia suggests a pathogenic role through the gut-brain axis, influencing neuroinflammatory and neurotransmitter pathways critical to psychotic, affective, and cognitive symptoms. Paradoxically, conventional psychotropic interventions may exacerbate this dysbiosis, with antipsychotics, particularly olanzapine, demonstrating profound effects on microbial architecture through disruption of bacterial phyla ratios, diminished taxonomic diversity, and attenuated short-chain fatty acid synthesis. To address these challenges, novel therapeutic strategies targeting the gut microbiome, encompassing probiotic supplementation, prebiotic compounds, faecal microbiota transplantation, and rationalised co-pharmacotherapy, show promise in attenuating antipsychotic-induced metabolic disruptions while enhancing therapeutic efficacy. Harnessing such insights, precision medicine approaches promise to transform antipsychotic prescribing practices by identifying patients at risk of metabolic side effects based on their microbial profiles. This IUPHAR review collates the current literature landscape of the gut-brain axis and its intricate relationship with schizophrenia while advocating for integrating microbiome assessments and therapeutic management. Such a fundamental shift in proposing microbiome-informed psychotropic prescriptions to optimise therapeutic efficacy and reduce adverse metabolic impacts would align antipsychotic treatments with microbiome safety, prioritising 'gut-neutral' or gut-favourable drugs to safeguard long-term patient outcomes in schizophrenia therapy.