Investigating the Clinical Effects and Mechanistic Underpinnings of Probiotics on Major Depressive Disorder

Abstract

Background: Probiotics have been hypothesized to improve symptoms of Major Depressive Disorder (MDD). Evidence suggests that these outcomes may be driven by probiotics reducing inflammation and regulating neurotransmission through the gut-brain axis. Objectives: 1) Systematically review the current literature on the effects of probiotics in mental health in humans; 2) Examine the efficacy, safety, and tolerability of a probiotic supplement on depression in a pilot study; 3) Develop a protocol for a double-blind randomized placebo-controlled trial to examine the effects of a probiotic supplement on depression; 4) Compare the clinical effects of a probiotic supplement versus placebo on depression to determine whether probiotics may have a role in alleviating symptoms of depression; 5) Examine molecular and microbial activity for possible mechanistic underpinnings of the relationship between probiotics and depression. Methods: I started by systematically reviewing the literature to evaluate the current state of the evidence and identify areas for further examination. I then implemented an 8-week open-label pilot study examining the effects of a probiotic supplement containing Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 on symptoms of depression in treatment-naïve adults diagnosed with MDD. Using data and knowledge acquired from the pilot work, I developed a protocol for a 16-week double-blinded randomized placebo-controlled trial (DBRCT) to further examine these effects and explore potential blood-based biomarkers and microbiome composition for response predictors and underlying mechanisms. Results: My systematic review of the literature revealed promising preliminary evidence for probiotics alleviating symptoms of depression but highlighted significant gaps and inconsistencies in the current literature. In our pilot work, we observed significant improvements in depressive symptoms following probiotic supplementation. However, findings from our DBRCT did not support the pilot findings. We found that probiotics were no superior to placebo in reducing depressive symptoms which was reflected in no significant group differences in blood-based biomarkers. However, building off our pilot work, analyses revealed potentially important differences in microbiome composition between probiotic responders and non-responders. Conclusions: These findings add to the growing body of research in this emerging field and provide crucial direction for developing future studies to examine the relationship between probiotics and MDD.