No abstract

Background: Gut and oral microbiota are intrinsically linked to human health. Recent studies suggest a direct link with mental health through bidirectional gut–brain pathways. Emerging evidence suggests that the composition and/or function of intestinal microbiome differs in those with psychosis and schizophrenia as compared with controls. There is relatively little research on the predicted or actual functional alterations associated with the composition of oral and gut microbiota in patients with psychosis. We will perform a systematic review and meta-analysis to identify, evaluate and if possible, combine the published literature on compositional alterations in the oral and gut microbiota in patients with psychosis or schizophrenia compared with healthy controls. We also aim to explore the potential functional impact of any compositional changes. Methods: Original studies involving humans and animals using a case-control, cohort or cross-sectional design will be included. The electronic databases PsycINFO, EMBASE, Web of Science, PubMed/MEDLINE and Cochrane will be systematically searched. Quantitative analyses will be performed using random-effects meta-analyses to calculate mean difference with 95% confidence intervals. Discussion: Changes in microbiota composition in psychosis and schizophrenia have been correlated with alternations in brain structure and function, altered immunity, altered metabolic pathways and symptom severity. Changes have also been identified as potential biomarkers for psychosis that might aid in diagnosis. Understanding how predicted or actual functional alterations in microbial genes or metabolic pathways influence symptomatic expression and downstream clinical outcomes may contribute to the development of microbiome targeted interventions for psychosis. Registration: The study is prospectively registered in PROSPERO, the International Prospective Register of Systematic Reviews (CRD42021260208).

Background and Hypothesis Intestinal microbiota is intrinsically linked to human health. Evidence suggests that the composition and function of the microbiome differs in those with schizophrenia compared with controls. It is not clear how these alterations functionally impact people with schizophrenia. We performed a systematic review and meta-analysis to combine and evaluate data on compositional and functional alterations in microbiota in patients with psychosis or schizophrenia. Study design Original studies involving humans and animals were included. The electronic databases PsycINFO, EMBASE, Web of Science, PubMed/MEDLINE, and Cochrane were systematically searched and quantitative analysis performed. Study results Sixteen original studies met inclusion criteria (1376 participants: 748 cases and 628 controls). Ten were included in the meta-analysis. Although observed species and Chao 1 show a decrease in diversity in people with schizophrenia compared with controls (SMD = −0.14 and −0.66 respectively), that did not reach statistical significance. We did not find evidence for variations in richness or evenness of microbiota between patients and controls overall. Differences in beta diversity and consistent patterns in microbial taxa were noted across studies. We found increases in Bifidobacterium, Lactobacillus, and Megasphaera in schizophrenia groups. Variations in brain structure, metabolic pathways, and symptom severity may be associated with compositional alterations in the microbiome. The heterogeneous design of studies complicates a similar evaluation of functional readouts. Conclusions The microbiome may play a role in the etiology and symptomatology of schizophrenia. Understanding how the implications of alterations in microbial genes for symptomatic expression and clinical outcomes may contribute to the development of microbiome targeted interventions for psychosis.