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Cited by 499Probiotics and Fermented FoodsTryptophan and brain disordersGut microbiota and health

Probiotic Lactobacillus plantarum 299v decreases kynurenine concentration and improves cognitive functions in patients with major depression: a double-blind, randomized, placebo controlled study

Rudzki, Leszek, Ostrowska, Lucyna, Pawlak, Dariusz, Małus, Aleksandra, Pawlak, Krystyna, Waszkiewicz, Napoleon, Szulc, Agata·2019·Psychoneuroendocrinology
DOI 10.1016/j.psyneuen.2018.10.010
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Abstract

Background Interactions between the digestive system and the brain functions have become in recent years an important field of psychiatric research. These multidirectional interactions take place in the so called microbiota-gut-brain axis and emerging scientific data indicate to the significant role of microbiota in the modulation of the central nervous system (CNS) including affective and cognitive functions.Objective An assessment of psychobiotic and immunomodulatory effects of probiotic bacteria Lactobacillus Plantarum 299v (LP299v) by measuring affective, cognitive functions and biochemical parameters in patients with MDD undergoing treatment with selective serotonin reuptake inhibitors (SSRI).Design Seventy nine patients with MDD were randomized and allocated to a double-blind, placebo-controlled trial. Participants received either a SSRI with the probiotic LP299v (n = 40) for a period of 8 weeks or a SSRI with the placebo of the probiotic (n = 39) for the same period. The severity of psychiatric symptoms was assessed using Hamilton Depression Rating Scale (HAM-D 17), Symptom Checklist (SCL-90) and Perceived Stress Scale (PSS-10). Cognitive functions were assessed using the Attention and Perceptivity Test (APT), Stroop Test parts A and B, Ruff Figural Fluency Test (RFFT), Trail Making Test (TMT) Parts A and B and the California Verbal Learning Test (CVLT). Biochemical parameters such as tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxykynurenine (3HKYN), anthranilic acid (AA), 3-hydroxy anthranilic acid (3HAA), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin 1-beta (IL-1b) and cortisol plasma concentrations were measured.Results Sixty participants finished the study and were analyzed: 30 participants in the LP299v group and 30 participants in the placebo group. There was an improvement in APT and in CVLT total recall of trials 1-5 in the LP299v group compared with the placebo between baseline and after 8 weeks of intervention. There was a significant decrease in KYN concentration in the LP299v group compared to the placebo group. We also observed significant increase in 3HKYN:KYN ratio in the LP299v group compared with the placebo group. Additionally, Repeated Measures ANOVA revealed a significant effect of interaction of Treatment x time for AA concentration. However, results of post hoc analysis did not reach statistical significance in neither probiotic nor placebo group. There were no significant changes of TNF-α, IL-6 and IL-1b and cortisol concentrations in neither probiotic nor placebo groups.Conclusions Augmentation of SSRI treatment with probiotic bacteria Lactobacillus Plantarum 299v improved cognitive performance and decreased KYN concentration in MDD patients. Decreased KYN concentration could contribute to the improvement of cognitive functions in the LP299v group compared to the placebo group. To our knowledge results of this study are the first evidence of improvement of cognitive functions in MDD patients due to probiotic bacteria and this is the first evidence of decreased KYN concentration in MDD patients due to probiotic bacteria.

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Crossref · 10.1016/j.psyneuen.2018.10.010

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  • 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 [399]

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Authors
Rudzki, L., Ostrowska, L., Pawlak, D., Małus, A., Pawlak, K., Waszkiewicz, N., & Szulc, A.
Affiliations
  • Medical University of Białystok (PL)
  • Medical University of Warsaw (PL)
Corresponding author
Rudzki, Leszek
ORCID
Venue
Psychoneuroendocrinology
Publisher
Elsevier BV
Published
2019-02
Volume
100
Pages
213-222
ISSN
0306-4530 (ISSN-L)
DOI
10.1016/j.psyneuen.2018.10.010
OpenAlex
W2897492348
Cited by
499
References
46
Citations by year
2026: 50 · 2025: 85 · 2024: 80 · 2023: 74 · 2022: 73 · 2021: 65 · 2020: 51 · 2019: 18 · 2018: 3
FWCI
32.15
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Psychoneuroendocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Medical University of Bialystok, Poland
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
Lactobacillus plantarum 299v, probiotics, major depressive disorder, kynurenine, microbiota-gut-brain axis, psychobiotics, cognitive function, selective serotonin reuptake inhibitors, tryptophan metabolism, neuroinflammation, cortisol, kynurenic acid, 3-hydroxykynurenine, interleukin-6
MeSH terms
Adult, Attention, Cognition, Combined Modality Therapy, Depressive Disorder, Major, Major Depressive Disorder, Double-Blind Method, Female, Humans, Kynurenine, Male, Middle Aged, Placebos, Down-Regulation, Treatment Outcome, Selective Serotonin Reuptake Inhibitors, Probiotics, Lactobacillus plantarum, Lactiplantibacillus plantarum

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