Gut microbial signatures in schizophrenia include significantly lower archaeal α-diversity and distinct β-diversity differences across archaea, fungi, and bacteria, with functional differences concentrated in glucose, lipid and amino acid metabolic pathways, and potential diagnostic biomarker panels achieving AUCs of 0.73, 0.69, and 0.74 for archaea, fungi, and bacteria respectively.
Study included 61 SCH patients and 69 healthy controls (HC)
Metagenomic shotgun sequencing (MSS) was used to analyze gut microbiota
The reduction in α-diversity was specific to archaea among the microbial kingdoms examined
No equivalent α-diversity reduction was reported for fungi or bacteria in the abstract
Results
Significant β-diversity differences between SCH patients and HC were found at the species level for all three microbial kingdoms: archaea, fungi, and bacteria.
β-diversity analysis was conducted at the species level for archaea, fungi, and bacteria
All three microbial groups showed significant compositional differences between SCH and HC
Analysis was performed using metagenomic shotgun sequencing on stool samples
Sample sizes were 61 SCH patients and 69 healthy controls
Results
Functional differences between SCH patients and HC were concentrated in glucose, lipid, and amino acid metabolic pathways.
Functional alterations were analyzed using metagenomic shotgun sequencing data
Three major metabolic pathway categories were implicated: glucose metabolism, lipid metabolism, and amino acid metabolism
Functional differences were observed across the gut microbiome broadly, not limited to one microbial kingdom
These functional findings were derived from compositional differences in archaea, fungi, and bacteria combined
Results
A panel of 9 archaeal species achieved an AUC of 0.73 for distinguishing SCH patients from healthy controls.
The diagnostic model was built using 9 archaeal species as potential biomarkers
AUC = 0.73 for the archaeal diagnostic panel
The model was developed to differentiate SCH patients (n=61) from HC (n=69)
This represents a novel contribution as archaeal gut microbiome signatures in SCH had been poorly addressed previously
Results
A panel of 8 fungal species achieved an AUC of 0.69 for distinguishing SCH patients from healthy controls.
The diagnostic model was built using 8 fungal species as potential biomarkers
AUC = 0.69 for the fungal diagnostic panel
The model was developed to differentiate SCH patients (n=61) from HC (n=69)
Fungal gut microbiome signatures in SCH had been poorly addressed prior to this study
Results
A panel of 22 bacterial species achieved an AUC of 0.74 for distinguishing SCH patients from healthy controls.
The diagnostic model was built using 22 bacterial species as potential biomarkers
AUC = 0.74 for the bacterial diagnostic panel, the highest among the three kingdoms tested
The bacterial panel contained the largest number of species (22) compared to archaeal (9) and fungal (8) panels
The model was developed to differentiate SCH patients (n=61) from HC (n=69)
Background
Gut microbial dysbiosis in schizophrenia has been demonstrated previously mainly for bacteria, but signatures of minority gut microbiota such as archaea and fungi had been poorly addressed.
The study was motivated by a gap in knowledge regarding non-bacterial gut microbiota in SCH
Prior research focused predominantly on bacterial dysbiosis in SCH
This study used metagenomic shotgun sequencing to comprehensively analyze archaea, fungi, and bacteria simultaneously
The trial was registered in Chinese Clinical Trial Registry: ChiCTR2000032118, registration date: 2020/04/20
Fu R, Liang X, Yang W, Li R, Shi Y, Guo L, et al.. (2026). Gut microbial signatures in schizophrenia: exploring archaea, fungi, and bacteria.. BMC psychiatry. https://doi.org/10.1186/s12888-025-07721-3