Effect of probiotic and prebiotic vs placebo on psychological outcomes in patients with major depressive disorder: A randomized clinical trial

Background: Disturbance in the equilibrium of the gut microbiota has been involved in the pathophysiology of depression. Probiotics have the potential to healthfully modulate the gut microbiome. Prebiotics could also be effective by stimulation of growth of some bacterial species in the gut microbiota. Objective: The aim of this double blind clinical trial, was to compare the effect of supplementation with the probiotic and prebiotic on the Beck Depression Inventory (BDI) score as a primary outcome as well as the kynurenine/tryptophan ratio and tryptophan/branch chain amino acids (BCAAs) ratio as secondary outcomes in patients with major depressive disorder (MDD). Design: One hundred and ten depressed patients were randomly assigned to receive the probiotic (Lactobacillus helveticus and Bifidobacterium longum), prebiotic (galactooligosaccharide) or placebo for 8 weeks. Serum tryptophan and BCAAs were measured by HPLC, and kynurenine by ELISA kit. Dietary intake and physical activity of the participants were recorded at baseline. Results: A total of 81 subjects (aged 36.5 +/- 8.03 y; mean (95% CI), 2.27 (1.76-2.93) y of depression duration) completed the trial (28 in the probiotic group, 27 in the prebiotic group, and 26 in the placebo group). From baseline to 8 weeks, probiotic supplementation resulted in a significant decrease in BDI score (17.39-9.1) compared to the placebo (18.18-15.55) and prebiotic (19.72-14.14) supplementation (p = 0.042). Inter-group comparison indicated no significant differences among the groups in terms of serum kynurenine/tryptophan ratio and tryptophan/BCAAs ratio. However, the kynurenine/tryptophan ratio decreased significantly in the probiotic group compared to the placebo group after adjusting for serum isoleucine (p = 0.048). In addition, the tryptophan/isoleucine ratio increased significantly in the probiotic group when compared to the placebo group (p = 0.023). Conclusion: Overall, 8 weeks of probiotic supplements to subjects with MDD resulted in an improvement in BDI score compared with placebo whereas no significant effect of prebiotic supplementation was seen. Study was registered in IRCT.ir under IRCT2015092924271N1. (C) 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.