Long Chen,1– 3 Wenzheng Li,1– 3 Daming Mo,1– 3 Xiaojing Meng,1– 3 Lihui Yao,1– 3 Xulai Zhang,1– 3 HuanZhong Liu4– 6 

1Department of Psychiatry, Hefei Fourth People’s Hospital, Hefei, People’s Republic of China; 2Department of Psychiatry, Affiliated Psychological Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3Department of Psychiatry, Anhui Mental Health Center, Hefei, People’s Republic of China; 4Department of Psychiatry, Chao Hu Hospital of Anhui Medical University, Hefei, People’s Republic of China; 5Anhui Provincial Key Laboratory for Brain Bank Construction and Resource Utilization, Hefei, People’s Republic of China; 6Department of Psychiatry. Anhui Psychiatric Center, Hefei, People’s Republic of China

Correspondence: Xulai Zhang, Email xulaizhang@163.com HuanZhong Liu, Email huanzhongliu@ahmu.edu.cn

Background: Schizophrenia (SZ) is a complex, multifactorial neurodevelopmental disorder characterized as a severe mental illness. Despite extensive research, its etiology and pathogenesis remain largely elusive. Recent studies suggest that the intestinal microbiota and its metabolites may play critical roles in the onset and regulation of SZ. This study aims to examine the characteristics of the intestinal microbiota and metabolomics in patients with SZ and to explore their correlation with clinical symptoms.
Methods: This study involved thirty-five patients diagnosed with schizophrenia (SZ group) and thirty healthy control participants (HC group). Fecal samples were collected and analyzed using microbiome (16S rRNA gene sequencing) and metabolome (UPLC-MS) techniques. Bioinformatics and statistical analyses were conducted to interpret the data.
Results: Age, sex, and BMI were comparable between the SZ and HC groups. Microbial diversity sequencing identified 837 operational taxonomic units (OTUs) across both groups. Although alpha diversity metrics showed no significant difference, beta diversity metrics revealed notable disparities. At the genus level, differences were observed in nine bacterial groups: Turicibacter, Toprococcus, Campylobacter, Eubacterium, Blautia, Sarcina, Catenibacterium, Lactobacillus, and Porphyromonas. At the family level, Erysipelotrichaceae, Turicibacteraceae, Campylobacteraceae, Desulfovibrionaceae, Lactobacillaceae, and Lachnospiraceae showed significant variations. Metabolomics analysis identified 946 metabolites, with 54 showing significant differences, primarily in caffeine metabolism and cysteine and methionine metabolism. Notably, correlations were found between differential gut microbes and metabolites, and between these metabolites and psychiatric clinical symptoms.
Conclusion: The study reveals significant abnormalities in the intestinal flora and metabolites of SZ patients, correlating with clinical severity. These findings offer new insights into the interactions between the gut microbiome and metabolites, potentially contributing to the understanding of the pathophysiology of schizophrenia.

Keywords: schizophrenia, gut microbiota, intestinal metabolites, 16S rRNA, UPLC-MS