Efficacy of Probiotic Supplementation with Lactobacillus and Bifidobacterium in Major Depressive Disorder: A Meta-analysis of Randomized Controlled Trials
K. M. Henry Moore, N. M. Neves, G. Stutz Francisco Moreira, A. Mert, J. Rodrigues Lopes, D. Soler Lopes, T. Pereira MendesIntroduction
Major depressive disorder (MDD) is a leading cause of global disability, often resistant to standard treatments. Increasing evidence implicates the gut–brain axis in its pathophysiology. Probiotics, especially Lactobacillus and Bifidobacterium strains, may exert antidepressant effects by modulating inflammation, neurotransmission, and the hypothalamic–pituitary–adrenal axis through their interaction with the gut microbiota.
Objectives
This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the efficacy of Lactobacillus - and Bifidobacterium -based probiotic supplementation in reducing depressive symptoms in individuals with MDD.
Methods
We searched PubMed, Embase, and the Cochrane Library for RCTs comparing probiotic supplementation to placebo or standard therapy in adults with MDD. Included studies used validated depression scales such as the Hamilton Depression Rating Scale (HAMD), Beck Depression Inventory (BDI), or Depression Anxiety Stress Scales (DASS). The primary outcome was change in depressive symptom severity. A random-effects model (Hartung-Knapp-Sidik-Jonkman method) was used to compute standardized mean differences (SMDs) with 95% confidence intervals (CIs). Exploratory subgroup analyses were conducted based on probiotic formulation, dosage, and strain composition.
Results
Eight RCTs with 539 participants were included. Of these, 279 patients (51.8%) received probiotic supplementation and 260 (48.2%) received placebo or standard therapy alone. Probiotic use was associated with a greater, though non-significant, reduction in depressive symptoms (SMD –0.34; 95% CI: –0.76 to 0.09; I² = 75%; Image 1). Subgroup analysis suggested larger effects with multistrain formulations and capsule-based delivery.
Image 1: Long description.