An emerging body of literature demonstrates differences in the gut microbiome (GMB) of patients with major depressive disorder (MDD) compared to healthy controls (HC), as well as the potential benefits of prebiotic, probiotic, and synbiotic treatment. We conducted a systematic review of 24 observational studies (n = 2817), and 19 interventional trials (n = 1119). We assessed alpha diversity, beta diversity, and taxa abundance changes in patients with MDD relative to HC, as well as the effect of prebiotics, probiotics, and synbiotics on depressive symptoms in individuals with clinical or subclinical depression. We observed no significant differences in alpha diversity but a significant difference in beta diversity between patients with MDD and HC. There were fluctuations in the abundance of specific taxa in patients with MDD relative to HC. Probiotic and synbiotic, but not prebiotic, treatment showed a modest benefit in reducing depressive symptoms in patients with MDD over four to nine weeks. The GMB profiles of patients with MDD differ significantly from HC, but further studies are needed to elucidate the benefits of prebiotic, probiotic and synbiotic treatments relative to antidepressants and over longer follow-up before these therapies are implemented into clinical practice.

The gut microbiome (GMB) plays an important role in developmental processes and has been implicated in the etiology of psychiatric disorders. However, the relationship between GMB and schizophrenia remains unclear. In this article, we review the existing evidence surrounding the gut microbiome in schizophrenia and the potential for antipsychotics to cause adverse metabolic events by altering the gut microbiome. We also evaluate the current evidence for the clinical use of probiotic and prebiotic treatment in schizophrenia. The current data on microbiome alteration in schizophrenia remain conflicting. Longitudinal and larger studies will help elucidate the confounding effect on the microbiome. Current studies help lay the groundwork for further investigations into the role of the GMB in the development, presentation, progression and potential treatment of schizophrenia.

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 nominal associations between select microbial features and clinical measures, including Positive and Negative Syndrome Scale (PANSS) scores and gastrointestinal symptoms. Predicted functional pathway analysis suggested alterations in microbial metabolic potential consistent with a metabolically stressed, pro-inflammatory microbiome. Conclusions: Individuals with clozapine-treated TRS demonstrate differences in gut microbiome composition compared to HC and are predicted to have some functional consequences relating to metabolic potential. These findings remain exploratory but contribute to a limited but growing body of literature in this clinically relevant population and provide a basis for longitudinal studies with appropriate comparator groups to better characterize these relationships and assess their clinical relevance.