Interfacing Genetics and Oral Microbiota in Schizophrenia: A Mechanistic Review of Bidirectional Neuroimmune Pathways

Schizophrenia is a debilitating psychiatric disorder affecting about 1% of the global population. It is typically characterized by symptoms like hallucinations, delusions, cognitive impairments, and emotional dysregulation. This study investigates the role of the oral microbiome in schizophrenia, emphasizing how oral microbiota disturbances (dysbiosis) may influence neuroinflammation and immune dysfunction, contributing to the disease. We aim to provide insight into the intricate relationship between the microbiome, genetics, and neuroimmune pathways involved in schizophrenia. A review was conducted to gather articles and research papers from scientific databases such as PubMed, Google Scholar, and Scopus. The search focused on articles published within the last decade, using keywords like “oral microbiome and schizophrenia,” “immune modulation,” “neuroinflammation in schizophrenia,” and “microbiome and neuroimmune pathways.” Studies were selected based on their relevance to the oral microbiome’s role in systemic and central nervous system inflammation, immune gene regulation, and its interactions with neurotransmitter systems in schizophrenia. Evidence suggests that disturbances in the oral microbiota can activate pro-inflammatory cytokines, influencing the blood-brain barrier and promoting neuroinflammation, which is central to schizophrenia. Genetic predispositions and immune system variations also play a significant role in modulating the microbiome, exacerbating neuroimmune dysfunction. Dysbiosis affects neurotransmitter regulation, including dopamine and glutamate, which are critical to schizophrenia pathophysiology. The oral microbiome significantly impacts immune regulation and neuroinflammatory processes in schizophrenia. This integrated approach, combining genetics, microbiome science, and neuroimmune pathways, opens new avenues for microbiome-based therapeutic interventions. By targeting the oral microbiome, it may be possible to reduce inflammation and improve schizophrenia symptoms, paving the way for more personalized treatment strategies. • Disturbances in the oral microbiome contribute to systemic and neuroinflammation involved in schizophrenia pathogenesis. • Immune dysregulation driven by oral microbial dysbiosis influences neurotransmitter systems such as dopamine and glutamate. • Host genetic variations shape oral microbiome composition and susceptibility to inflammation in schizophrenia. • Epigenetic changes, including DNA methylation and non-coding RNA regulation, link microbial signals to altered brain function. • Microbiome-based therapies targeting oral dysbiosis present promising adjunctive strategies for schizophrenia management.