Effect of probiotic and prebiotic vs placebo on psychological outcomes in patients with major depressive disorder: a randomized clinical trial
Abstract
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.
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The Phase II sample size was calculated using G*Power 3.1.9.7 for a two-way repeated-measures ANOVA with α=0.05, power=0.8, 3 groups, 4 measurements, and effect size 0.15, yielding 120 subjects (40 per group) including a 30% dropout rate.
“the estimated sample size required was computed using the G*Power 3.1.9.7 calculator to estimate sample size needed for two-way repeated measure ANOVA: the α error was 0.05, the power was 0.8, the number of groups was 3, the number of measurements was 4 and the effect size was 0.15 [28].”
Rosell®-52 and Rosell®-175 (daily intake of 10^10 CFU for 30 days) showed better results in alleviating depressed mood and pro-inflammatory cytokines among patients with depression compared with control subjects on placebo.
“In addition, Rosell®-52 and Rosell®-175 (daily intake of 1010 CFU for 30 days) showed better results in alleviating depressed mood and pro-inflammatory cytokines among patients with depression compared with control subjects on placebo [28].”
Two randomized controlled trials in people with clinical depression reported an altered kynurenine:tryptophan ratio and kynurenine concentrations after receiving a probiotic intervention compared with placebo.
“For example, two randomized controlled trials in people with clinical depression reported an altered kynurenine:tryptophan ratio and kynurenine concentrations after receiving a probiotic intervention compared with placebo (399, 400).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [400]
Various Lactobacillus strains, or Lactobacillus-containing supplements, have been shown to reduce depressive-like behaviour in rodents and improve measures of depression in humans.
“Various Lactobacillus strains, or Lactobacillus-containing supplements, have been shown to reduce depressive-like behaviour in rodents [1, 13, 23, 44, 45] and improve measures of depression in humans [3, 5, 39, 76].”
From Distinct actions of the fermented beverage kefir on host behaviour, immunity and microbiome gut-brain modules in the mouse (2020) · cites this paper as [39]
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- Authors
- Kazemi, A., Noorbala, A. A., Azam, K., Eskandari, M. H., & Djafarian, K.
- Affiliations
- Tehran University of Medical Sciences (IR)
- Imam Khomeini Hospital (IR)
- Shiraz University (IR)
- Corresponding author
- Kazemi, Asma
- Noorbala, Ahmad Ali
- Azam, Kamal
- Eskandari, Mohammad Hadi
- Djafarian, Kurosh
- Venue
- Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 38
- Issue
- 2
- Pages
- 522-528
- ISSN
- 0261-5614 (ISSN-L)
- OpenAlex
- W2799891707
- Cited by
- 534
- References
- 30
- Citations by year
- 2026: 52 · 2025: 75 · 2024: 82 · 2023: 94 · 2022: 77 · 2021: 67 · 2020: 49 · 2019: 31 · 2018: 6 · 2017: 1
- FWCI
- 35.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Tehran University of Medical Sciences (94-02-161-29551)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- major depressive disorder, probiotics, prebiotics, gut microbiota, Lactobacillus helveticus, Bifidobacterium longum, galactooligosaccharides, kynurenine/tryptophan ratio, depression severity, dietary intake
- MeSH terms
- Adult, Depressive Disorder, Major, Major Depressive Disorder, Double-Blind Method, Female, Humans, Male, Treatment Outcome, Probiotics, Prebiotics
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