The Gut–Brain Axis and Psychosis: A Systematic Review of Microbial Metabolites and Their Impact on Dopaminergic Pathways in Schizophrenia

Schizophrenia is a psychiatric disorder that has psychotic, cognitive, and negative symptoms, with dopaminergic dysfunction.The gut-brain axis is identified as an important modulator for neurochemical function.Following PRISMA 2020 guidelines, this systematic review is conducted through searches (PubMed, Scopus, SpringerLink, Taylor & Francis, and Google Scholar).After removing duplicates and screening, six studies included three clinical studies, two translational studies involving fecal microbiota transplantation (FMT), and one rodent model.The findings highlighted three main themes:(1) the dysregulation of the tryptophan-kynurenine pathway, with elevated kynurenine and reduced kynurenic acid linked to disrupted dopaminergic and glutamatergic signaling; (2) changes of microbiota composition and metabolite imbalances, which included fewer butyrate producers and more succinate generators, which were associated with neurotransmitter dysregulations; and (3) relationships within clinical symptoms, in which metabolites correlated with comprehension of negative/cognitive deficits.Collectively, microbial dysbiosis and metabolite imbalance influence dopamine biosynthesis, receptor activity, immune, metabolic, and neurochemical signaling.