Blood Microbiome Analysis Reveals Biomarkers of Treatment Response in Drug-Naïve Patients with First-Episode Psychosis: A Pilot Study

Abstract

Patients with First-Episode Psychosis (FEP) exhibit variable responses to antipsychotic treatment. Emerging evidence suggests that disease-related dysbiosis of gut and oropharyngeal microbiota may lead to the abnormal translocation of microorganisms via the bloodstream. This study aims to explore the blood microbiome to identify candidate biomarkers associated with treatment outcomes in FEP. To address this, blood samples were collected from twenty drug-naïve individuals with FEP, both before and after four weeks of antipsychotic medication. DNA extracted from these samples underwent 16S rRNA gene sequencing and comprehensive bioinformatics analysis. Clinical assessments were based on the Positive and Negative Syndrome Scale and standard remission criteria. Peripheral cytokines (IL1β, TNF-α, IL10) were quantified by immunoassays. Baseline comparisons showed a significantly greater microbiome alpha diversity in remitters, along with differential prevalence in five taxa and 217 metabolic pathways. Post-treatment assessments uncovered a significantly distinct impact of antipsychotics on blood bacterial composition between remission groups, while initial differences on metabolic profiles persisted. Additionally, strong correlations were observed, linking specific taxa abundances to cytokine levels. Conclusively, this pilot study suggests that blood microbiome profiling could provide novel biomarkers for predicting therapeutic response in early psychosis, paving the way for precision medicine interventions.