Multi-Omics Analysis Reveals Aberrant Gut-Metabolome-Immune Network in Schizophrenia

Area of Science:

• Neuroimmunology
• Microbiome Research
• Metabolomics

Background:

• Schizophrenia (SCZ) is linked to immune system dysfunction, notably increased pro-inflammatory cytokines.
• Intestinal microbiota alterations are observed in SCZ patients.
• Microorganisms and their metabolites can modulate immune system activity.

Purpose of the Study:

• To systematically investigate the aberrant gut-metabolome-immune network in schizophrenia.
• To explore the correlations between gut microbiota, serum metabolome, and inflammatory cytokines in SCZ.
• To identify potential microbial-derived metabolites influencing immune responses in SCZ.

Main Methods:

• Integrative multi-omics analysis of intestinal microbiota, serum metabolome, and serum inflammatory cytokines.
• Comparison between 63 SCZ patients and 57 healthy controls.
• Development of a random forest model using omics data.

Main Results:

• Eighteen differentially abundant metabolite clusters were altered in SCZ patients, showing increased pro-inflammatory and decreased anti-inflammatory metabolites.
• Gut bacterial groups correlated more strongly with circulating metabolites than with cytokines.
• A model using seven serum metabolites accurately distinguished SCZ patients from controls (AUC=0.99), linked to cytokines and gut microbiota alpha-diversity.

Conclusions:

• An aberrant gut-metabolome-immune network exists in SCZ.
• Gut microbiota may influence immune responses by regulating host metabolic processes.
• Findings suggest microbial metabolites regulate inflammatory cytokines, offering insights for diagnosing and treating mental disorders.