Gut microbiome characteristics in individuals across different stages of schizophrenia spectrum disorders: A systematic review and meta-analysis

Schizophrenia (SCZ) is a complex neuropsychiatric disorder with unclear pathogenesis, limiting advances in early diagnosis and targeted interventions. Increasing evidence suggests that the gut microbiome contributed to SCZ pathophysiology, yet comprehensive characterization across illness stages remains lacking. This meta-analysis aimed to characterize gut microbial alterations across the SCZ spectrum disorder, including individuals at ultra-high risk for psychosis, first-episode psychosis (FEP) and chronic SCZ patients. A systematic search of 10 databases identified 91 case-control studies. Gut microbial outcome measures included relative abundance, alpha and beta diversity. Review Manager and R were used to analyze the data. The results showed that patients with SCZ exhibited significantly reduced alpha diversity, particularly in Shannon, Chao1, Observe and Evenness indices, compared to healthy controls. Beta diversity also differed significantly, with 88.5 % of studies reporting distinct microbial profiles across SCZ stages. Quantitative analysis revealed significantly increased relative abundance of Bacteroides and a decrease abundance of Bifidobacterium and Lactobacilli in FEP patients compared to healthy controls. Qualitative analysis further showed increasing abundance in Lactobacillus, Prevotella and Collinsella, but decreasing abundance in Faecalibacterium, Butyricicoccus, and Blautia in SCZ. Bifidobacterium exhibited stage-specific changes, decreasing in first-episode psychosis but increasing in chronic stages, while Bacteroides followed an opposite trajectory. Notably, Lactobacillus demonstrated an early upward tractor in high-risk individuals, persisting to chronic stages. This meta-analysis identified dynamic and consistent alterations in the gut microbial across the SCZ spectrum. These findings implicated the potentials of gut microbes as early indicators for identification and intervention of SCZ.