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.

<b><i>Background:</i></b> Emerging evidence suggests an important role of the human gut microbiome in psychiatry and neurodevelopmental disorders. An increasing body of literature based on animal studies has reported that the gut microbiome influences brain development and behavior by interacting with the gut-brain axis. Furthermore, as the gut microbiome has an important role in metabolism and is known to interact with pharmaceuticals, recent evidence suggests a role for the microbiome in antipsychotic-induced metabolic side effects in animals and humans. <b><i>Purpose:</i></b> Here we present the protocol for a two-phase study investigating the gut microbiome in healthy controls and in patients with schizophrenia treated with antipsychotics. <b><i>Methods:</i></b> Phase I of our study involves humans exclusively. We recruit 25 patients who are chronically treated with clozapine and compare them with 25 healthy controls matched for age, sex, BMI, and smoking status. A second cohort consists of 25 patients newly starting on clozapine, and a third cohort includes 25 antipsychotic-naive patients. The patients in the second cohort and third cohort are prospectively assessed for up to 6 and 12 weeks, respectively. Phase II of this study will incorporate microbiota humanized mouse models to examine the influence of human fecal transplant on metabolic parameters and the gut-brain axis. <b><i>Progress and Future Directions:</i></b> We are underway with the first participants enrolled in all phase I treatment cohorts. This study will contribute to elucidating the role of the gut microbiome in schizophrenia and metabolic side effects. In addition, its results may help to explore potential therapeutic targets for antipsychotic-induced metabolic side effects.