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Investigation of the Gut Microbiome in Treatment-Resistant Schizophrenia Compared to Healthy Controls: A Cross-Sectional Pilot Study: Étude du microbiome intestinal chez les patients atteints de schizophrénie résistante au traitement par rapport aux témoins sains : étude pilote transversale

Jonathan C. W. Liu, Ilona Gorbovskaya, Amy Y. Zhang, M. Hahn, G. De Palma, D. Müller

Canadian journal of psychiatry. Revue canadienne de psychiatrie, 2026

25 participants

Abstract

Background Schizophrenia (SCZ) is a debilitating disorder affecting approximately 1% of the Canadian population and remains a major contributor to disease burden and disability. Up to one-third of individuals with SCZ are affected by treatment-resistant SCZ (TRS). Clozapine remains the most effective treatment for TRS. However, its use is limited by serious metabolic and immune-related side effects. The gut microbiome may be a potential contributor to both SCZ pathology and antipsychotic-induced side effects, though studies examining this in the clozapine-treated TRS population remain limited. Methods This cross-sectional case-control study compared the gut microbiome composition of 25 TRS patients receiving long-term clozapine treatment to 25 healthy controls (HCs) matched for age, sex, body mass index, and smoking status. Participants provided fecal samples and completed assessments of psychiatric symptoms, eating behaviors, dietary intake, and metabolic measures. Fecal microbiome composition and predicted function were assessed using 16S rRNA gene sequencing (v3 region). Results Individuals with TRS being treated with clozapine presented with a distinct microbiome in comparison to HC, including reduced microbial diversity. Taxonomic analyses revealed reduced relative abundance of Firmicutes, while elevated relative abundance of Eggerthella spp., Mucispirillum spp., and unclassified species within the order SHA-98 (class Clostridia). Exploratory analyses also identified…

How strong is the evidence?

Evidence Hub reads this as a case-control, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause. Reported size: 25 participants or records.

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