The Gut–Brain Axis in Schizophrenia: A Systems-Level Understanding of Psychiatric Illness

Schizophrenia is a complex psychiatric disorder traditionally linked to neurotransmitter dysregulation, particularly within dopamine and glutamate pathways. However, recent evidence implicates the gut–brain axis as a potential contributor to its pathophysiology. This perspective article proposes a systems-level understanding of schizophrenia that incorporates the role of gut microbial dysbiosis specifically, reductions in short-chain fatty acid (SCFA)-producing taxa, and elevations in pro-inflammatory microbes. These imbalances may compromise gut barrier integrity, stimulate systemic inflammation, and disrupt neurochemical signaling in the brain. We synthesize findings from animal models, clinical cohorts, and microbial intervention trials, highlighting mechanisms such as SCFA regulation, altered tryptophan–kynurenine metabolism, and microbial impacts on neurotransmitters. We also explore microbiome-targeted interventions like probiotics, prebiotics, dietary strategies, and fecal microbiota transplantation (FMT) and their potential as adjunctive therapies. While challenges remain in causality and translation, integrating gut–brain axis insights may support more personalized and biologically informed models of schizophrenia care.