Gut-brain connection in schizophrenia: A narrative review

Abstract

Schizophrenia is a complex neuropsychiatric disorder characterized by cognitive, emotional, and behavioral impairments. The microbiota-gut-brain axis is crucial in its pathophysiology, mediating communication between the gut and brain through neural, immune, endocrine, and metabolic pathways. Dysbiosis, or an imbalance in gut microbiota, is linked to neuroinflammation, systemic inflammation, and neurotransmitter disruptions, all of which contribute to the symptoms of schizophrenia. Gut microbiota-derived metabolites, such as short-chain fatty acids, influence brain function, including immune responses and neurotransmitter synthesis. These findings suggest that microbial imbalances exacerbate schizophrenia, providing a novel perspective on the disorder's underlying mechanisms. Emerging microbiota-targeted therapies-such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation-show promise as adjunctive treatments, aiming to restore microbial balance and improve clinical outcomes. While further research is needed, targeting the microbiota-gut-brain axis offers an innovative approach to schizophrenia management, with the potential to enhance patient outcomes and quality of life.

Keywords: Gut-brain axis; Microbiota; Neuroinflammation; Probiotics; Schizophrenia.

Figure 1

Gut-brain axis and roles of the vagus nerve and the enteric nervous system in brain function and their relevance to schizophrenia. The vagus nerve regulates feeding and autonomic nervous system activity and transmits gut-derived signals to the brain, influencing mood and cognition. The enteric nervous system controls local gut function, modulates immune interactions, and communicates with the brain while mediating microbiota interactions. Disruptions in these pathways, including altered gut-brain signaling, immune activation, and microbiota imbalances, have been linked to neuropsychiatric disorders such as schizophrenia and autism spectrum disorder. GI: Gastrointestinal; ASD: Autism spectrum disorder.

Figure 2

Tryptophan metabolism. Tryptophan can be metabolized into serotonin or kynurenine (this process is influenced by gut microbiota and inflammation/stress). Inflammation or stress shifts tryptophan metabolism toward the kynurenine pathway. Serotonin helps in mood regulation, sleep cycle, and cognitive function. Quinolinic acid is a neurotoxin, while kynurenic acid is neuroprotective.