Altered gut microbiota and untargeted metabolomic features in patients with schizophrenia: a case–control study
Abstract
Mental disorders are among the leading causes of global disease burden, and their etiology spans genetic, environmental, and physiological factors. Emerging evidence suggests that the gut microbiota may contribute to the development of neuropsychiatric disorders through the microbiota–gut–brain axis. This study aimed to characterize differences in gut microbial composition and untargeted metabolomic profiles between patients with schizophrenia and healthy controls. Fecal samples were collected from 30 patients with schizophrenia and 30 healthy controls; 59 samples (30 patients and 29 controls) yielded qualified 16S rRNA gene sequencing data. Untargeted metabolomic profiling was performed by ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS). Compared with healthy controls, patients with schizophrenia showed reduced microbial richness and diversity together with marked separation in β-diversity. In an exploratory random forest ranking, Pseudocitrobacter, Hafnia-Obesumbacterium, and Escherichia-Shigella contributed most strongly to between-group discrimination. Escherichia-Shigella was significantly enriched in patients (median relative abundance 2.377% in group S vs. 0.119% in group H; q = 0.00031; Cliff’s δ = 0.646), whereas Faecalibacterium (2.630% vs. 7.275%) and Agathobacter (0.903% vs. 2.874%) were more abundant in healthy controls. Untargeted metabolomics likewise revealed between-group differences that predominantly involved metabolites and pathways of amino acid and lipid metabolism. Patients with schizophrenia show alterations in gut microbial composition and untargeted metabolomic features, supporting an association between schizophrenia and microbiota–metabolite alterations. Future confirmation requires larger longitudinal cohorts and independent validation datasets. Owing to the small sample size, cross-sectional study design, and antipsychotic drug exposure, we could not disentangle disease-specific effects from medication-related effects.