Schizophrenia (SCZ) is a multifaceted psychiatric condition with a complex set of etiological factors. Recent studies have revealed that gut microbiota play a significant role in the neurobiology associated with SCZ. Utilizing metagenomic sequencing and analysis techniques, we obtained composition and functional information of the gut microbiota from 68 SCZ patients and 61 healthy control (HC) subjects. We identified 72 inter-group differential species, 49 differential metabolic pathways, and 1987 differential functional genes. A. odontolyticus and F. prausnitzii were the core species enriched in the SCZ group and the HC group, respectively. Arginine and proline metabolism were the most significant differential metabolic pathways, with K00286 being the differential functional gene catalyzing the synthesis of L-proline in this pathway. Notably, a strong disease classification model was developed based on the gut microbiota data, achieving an outstanding AUC of 0.94, outperforming earlier models, the model achieved AUC values of 0.745 and 0.845 in two separate external datasets, respectively. Furthermore, insights into mechanisms were investigated by analyzing the relationships between microbial species and their associated metabolic pathways. Future research is essential to clarify causal connections, detail specific molecular pathways—particularly those involving functional proteins such as K00286—and to explore the communication processes between the gut microbiota and the brain. Our results underscore the potential for microbiota-based biomarkers and therapeutic targets in SCZ, emphasizing the essential role of gut microbiota in this intricate disorder.
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