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

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. 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). 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. 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. 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.

Rudzki L ，Ostrowska L ，Pawlak D ，Małus A ，Pawlak K ，Waszkiewicz N ，Szulc A ... -  《-》

Probiotic Lactobacillus plantarum 299v supplementation in patients with major depression in a double-blind, randomized, placebo-controlled trial: A metabolomics study.

Godzien J ，Kalaska B ，Rudzki L ，Barbas-Bernardos C ，Swieton J ，Lopez-Gonzalvez A ，Ostrowska L ，Szulc A ，Waszkiewicz N ，Ciborowski M ，García A ，Kretowski A ，Barbas C ，Pawlak D ... -  《-》

The effect of prebiotic supplementation on serum levels of tryptophan and kynurenine in obese women with major depressive disorder: a double-blinded placebo-controlled randomized clinical trial.

The objective of the present study was to examine the effect of calorie restricted diet (CRD) plus inulin supplementation on serum levels of tryptophan (Trp), kynurenine (Kyn) and Trp/Kyn ratio in obese women with major depressive disorder (MDD). In this double-blind placebo-controlled randomized clinical trial, 51 obese women (BMI = 30-40 kg/m2) with mild MDD were assessed for depression level using Hamilton depression rating scale (HDRS). The patients were randomly allocated into either "Prebiotic group" (received 10 g/day inulin) or "Placebo group" (received 10 g/day maltodextrin). All participants also received individualized CRD. Fasting serum levels of Trp, Kyn, and Trp/Kyn ratio were assessed at baseline and after 8 weeks. Results showed slightly greater increases in serum levels of Trp and Trp/Kyn ratio as well as reductions in serum level of Kyn and HDRS score in prebiotic group than placebo group. However, between group differences in these parameters as well as HDRS score were not statistically significant after adjusting for baseline variables at the end of the trial. Results indicates that CRD accompanied by inulin supplementation (10 g/day) did not influence serum levels of Trp, Kyn and Trp/Kyn ratio as well as HDRS score after 8 weeks. The trial was registered in the Iranian registry of clinical trials at 2018-08-02 ( https://www.irct.ir/ ; registration number: IRCT20100209003320N15).

Khademi F ，Tutunchi H ，Vaghef-Mehrabani E ，Ebrahimi-Mameghani M ... -  《-》

Cross-sectional relationship between kynurenine pathway metabolites and cognitive function in major depressive disorder.

Cognitive impairment is common among patients with major depressive disorder (MDD), but its pathological mechanism is complex and not fully understood. Evidence suggests that the kynurenine (KYN) pathway may be implicated in the pathophysiology of depression, but few studies have explored the association between the KYN pathway and cognitive impairment in MDD. Our aim was to examine the relationship between cognitive impairment and KYN pathway metabolites in patients with MDD. A total of 146 patients with MDD according to DSM-V and 72 healthy controls (HCs) were enrolled, and the severity of depressive symptoms using the 17-item Hamilton Depression Rating Scale (HAMD-17) and cognitive performance including speed of processing, working memory, visual learning and verbal learning were assessed. Blood samples were collected, and serum concentrations of tryptophan (TRP), kynurenine (KYN) and kynurenic acid (KYNA) were measured by liquid chromatography-tandem mass spectrometry. In females with MDD, there was a significant negative association between the KYN level and verbal learning (B=-0.039, adjusted p = 0.018), and the KYN/TRP ratio was negatively correlated with speed of processing (B=-470.086, adjusted p = 0.029), verbal learning (B=-544.251, adjusted p = 0.002) and visual learning (B=-513.777, adjusted p = 0.004). Those associations were not present in male individuals with MDD or in HCs, except for a significant negative correlation between the KYNA/KYN ratio and category fluency (B=-0.373, adjusted p = 0.039) in female HCs. Our results suggest that learning function and speed of processing in female MDD were associated with KYN serum level and the KYN/TRP ratio, potentially implicating the KYN pathway in the pathological mechanism of cognitive function in female MDD.

Zhou Y ，Zheng W ，Liu W ，Wang C ，Zhan Y ，Li H ，Chen L ，Ning Y ... -  《-》

Effects of 4 weeks of Lactobacillus plantarum 299v supplementation on nutritional status, enteral nutrition tolerance, and quality of life in cancer patients receiving home enteral nutrition - a double-blind, randomized, and placebo-controlled trial.

Kaźmierczak-Siedlecka K ，Folwarski M ，Ruszkowski J ，Skonieczna-Żydecka K ，Szafrański W ，Makarewicz W ... -  《-》