The Safety, Efficacy, and Tolerability of Microbial Ecosystem Therapeutic-2 in People with Major Depression and/or Generallzed Anxiety Disorder

Abstract

Objective: The primary objective of this study is to assess subjective changes in mood and anxiety symptoms before, during, and after administration of the microbial therapeutic. The secondary objectives of this study are to assess changes in diversity of gut microbiome, changes in peripheral blood biomarkers, repopulation of healthy gut bacteria, and safety and tolerability of therapeutic. Method: Twelve adults diagnosed with major depressive disorder or generalized anxiety disorder were recruited from the Kingston area. Participants orally consumed once daily an encapsulated microbial therapeutic, containing 40 strains of bacteria purified and lab-grown from a single healthy donor stool, for 8 weeks. Participants underwent a series of clinical assessments measuring mood, anxiety, and gastrointestinal (GI) symptoms using validated clinical scales and questionnaires. Molecular data was collected from blood and fecal samples to assess metabolic changes, neurotransmitter, immunoglobulin, and inflammatory markers concentrations, and alpha diversity for fecal samples to predict outcomes in depression or anxiety. Results: Of the twelve individuals included in this study, nine have responded to treatment (50% improvement in MADRS and/or GAD-7 scores from baseline to week 8 visit). Over the course of 10 weeks MET-2 significantly decreased MADRS and GAD-7 scores, MADRS [F (5, 55) = 8.784, p<0.001 and F(2.78,30.56) = 9.638, p<0.01], respectively. This improvement may be mediated by the recolonization of the gastrointestinal tract with healthy bacteria resulting in increased bacterial diversity. Although increased bacterial diversity was seen in participants’ stool samples from baseline (3.62  0.20) to week 8 (3.69  0.13), this increase was not significant (p=0.104). Results for peripheral blood biomarkers showed a significant decrease in overall HDL, IgM, and IgG concentrations.No significant change was seen in alpha diversity during stool analysis. Conclusion: The findings of this study are the first to provide evidence for the role of microbial ecosystem therapy in treating depression and anxiety. However, a double-blind, randomized controlled trial with a larger sample size is needed for more conclusive results.