Altered gut microbiota and untargeted metabolomic features in patients with schizophrenia: a case–control study
- 1The 984th Hospital of Joint Logistics Support Force of the Chinese People’s Liberation Army
- 2The 8th Medical Center of the Chinese People’s Liberation Army General Hospital
Abstract
Background: 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.
Methods: 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).
Results: 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.
Conclusion: 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.
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BibTeX
@article{mi2026altered,
title = {{Altered gut microbiota and untargeted metabolomic features in patients with schizophrenia: a case–control study}},
author = {Yunqiang Mi and Peng Sun and Qingrui Hao and Yuanjun Yang and Chang Dong and Cunzhe Kong and Liqing Li and Chunhai Zhao and Hong Yin},
journal = {Frontiers in Psychiatry},
year = {2026},
month = oct,
doi = {10.3389/fpsyt.2026.1981601},
url = {https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1981601/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Altered gut microbiota and untargeted metabolomic features in patients with schizophrenia: a case–control study
AU - Yunqiang Mi
AU - Peng Sun
AU - Qingrui Hao
AU - Yuanjun Yang
AU - Chang Dong
AU - Cunzhe Kong
AU - Liqing Li
AU - Chunhai Zhao
AU - Hong Yin
PY - 2026
DA - 2026/10/22
JO - Frontiers in Psychiatry
DO - 10.3389/fpsyt.2026.1981601
UR - https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1981601/full
AB - Background: 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. Methods: 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). Results: 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. Conclusion: 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.
SN - 1664-0640
ER -