Gut microbial signatures in schizophrenia: exploring archaea, fungi, and bacteria

BACKGROUND: Gut microbial, mainly bacterial dysbiosis, has been demonstrated in patients with schizophrenia (SCH). However, the signatures and differences of minority gut microbiota in SCH, such as archaea and fungi, have been poorly addressed. METHODS: We obtained stool samples from 61 SCH patients and 69 healthy controls (HC), and analyzed the compositional and functional alterations of gut archaea, fungi, and bacteria using metagenomic shotgun sequencing (MSS). Additionally, we developed potential biomarkers to distinguish SCH from HC. RESULTS: SCH patients showed significantly lower archaeal α-diversity compared with that of HC. Whereas there were significant differences between SCH and HC in β-diversity at the species level of archaea, fungi and bacteria. Meanwhile, the functional differences between the two groups were concentrated in glucose, lipid and amino acid metabolic pathways. Furthermore, we established potential diagnostic archaeal (9 species, AUC = 0.73), fungal (8 species, AUC = 0.69), and bacterial (22 species, AUC = 0.74) microbiomes for differentiating SCH patients from HC. CONCLUSIONS: This study describes a more comprehensive understanding of abnormal gut microbiome in SCH and might provide candidate targets for the development of a microbe-based diagnosis for SCH. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000032118, registration date: 2020/04/20.