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Probiotic Lactobacillus Plantarum 299v decreases kynurenine concentration and improves cognitive functions in patients with major depression: A double-blind, randomized, placebo controlled study.
Rudzki, L, Ostrowska, L, Pawlak, D, Małus, A, Pawlak, K, Waszkiewicz, N, Szulc, A
Psychoneuroendocrinology. 2019;100:213-222
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Expert Review
Conflicts of interest:
None
Take Home Message:
- Significant improvement in cognitive performance and decreased l-tryptophan breakdown may be seen in patients on SSRI medication for depression, when supplemented with Lactobacillus Plantarum 299v.
- Work on microbiome diversity and gut barrier integrity may be important for psychiatric disorder support, including depression.
- More research is needed given small sample size and short trial period, with a focus on microbiome modulation over a longer period of time.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
This study sets out to explore the psychobiotic potential of the probiotic strain Lactobacillus Plantarum 299v (LP299v), a common single strain probiotic supplement. Depression symptoms, cognitive function and biochemical parameters were assessed in 79 patients with MDD undergoing conventional treatment with SSRIs in this double-blind placebo-controlled trial over a period of 8 weeks. Various outcome measures were used to assess the severity of depression and cognitive function, and various biochemical parameters such as tryptophan, kynurenine and cortisol were monitored. Results showed there was a significant decrease in kynurenine concentration and an improvement in cognitive function in the LP299v group compared to placebo.
Clinical practice applications:
The small sample size and short trial period of 8 weeks are limitations to this study, however, the results are important and certainly warrant more research in this area. A focus on microbiome modulation over a longer period of time may be useful to give us insight into the multidirectional interactions of the gastrointestinal microbiome and the central nervous system.
Considerations for future research:
This study suggests that patients being treated with SSRIs for MDD may see a significant improvement in cognitive performance and a decrease in the breakdown of the important amino acid l-tryptophan (from the decrease in kynurenine concentration results) if they supplement with LP299v alongside. Therefore, consideration of the microbiome and gut barrier integrity with regard to psychometric and biochemical parameters could be important to support psychiatric disorders, including depression.
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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The relationship between the leptin/ghrelin ratio and meals with various macronutrient contents in men with different nutritional status: a randomized crossover study.
Adamska-Patruno, E, Ostrowska, L, Goscik, J, Pietraszewska, B, Kretowski, A, Gorska, M
Nutrition journal. 2018;17(1):118
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Free full text
Plain language summary
Obesity is a chronic disease caused mostly by an excessive supply of energy delivered with food in relation to energy expenditure, which leads to fat accumulation. The aim of the study was to investigate the leptin/ghrelin ratio (appetite-regulating hormones) in response to meal intake with various macronutrient contents, and to assess the fasting and postprandial (after meal) differences between normal and overweight or obese men. The study is a crossover designed study which was conducted among 46 non-diabetic men. The participants were randomly divided into two groups. Each group included men with normal weight and overweight/obesity. Results indicate that in normal body weight men, a more beneficial leptin/ghrelin ratio was noted after the high-carbohydrate fat-free meal intake, compared to the normal-carbohydrate/high-protein and high-fat/low-carbohydrate meal. Furthermore, overweight/obese men presented with a significantly higher leptin/ghrelin ratio in a fasting state and after intake of each of the three meals. Authors conclude that overweight/obese individuals can be recommended to chose meals with lower carbohydrate content.
Abstract
BACKGROUND Hormones, which influence satiety and hunger, play a significant role in body energy balance regulation. Ghrelin is a peptide that plays an important role in short-term appetite regulation, whereas leptin is a factor that controls long-term energy balance and is considered as a satiety hormone. The aim of this study was to evaluate the leptin/ghrelin ratio in a fasting state and after the intake of meals with varying macronutrient contents and to assess the possible differences between normal body weight and overweight/obese men. METHODS We examined 46 healthy adult men (23 with normal body weight and 23 overweight/obese) aged 21-58, who were divided into two groups. In the crossover study, participants received isocaloric (450 kcal) meals with different macronutrient contents: men from the first group received high-carbohydrate (HC) and normo-carbohydrate (NC) meals, and in the second group, participants received high-carbohydrate and high-fat (HF) meals. The ratio of leptin/ghrelin levels was calculated from leptin and total ghrelin serum concentrations in a fasting state and 30, 60, 120, 180 and 240 min after meal intake. One-way ANOVA and Wilcoxon signed-rank tests were carried out. The normality of the variable distribution was checked with the Shapiro-Wilk test, the homogeneity of variances was verified with the Levene test, and the false discovery rate p-value adjustment method was used. RESULTS The leptin/ghrelin ratio was significantly higher in overweight/obese men than individuals with normal body weight in a fasting state, as well as postprandially. We observed trends towards a higher leptin/ghrelin ratio values from the 60 min after HC-meal intake compared to the NC- and HF-meals in normal body weight participants, while in overweight/obese men, we did not note any significant differences dependent on the meal type. CONCLUSIONS We have observed a significantly different postprandial leptin/ghrelin ratio in normal body weight and overweight/obese men, and our results suggest that in men with normal body weight, a greater feeling of satiety may occur after high-carbohydrate meal intake, which was not noted in the overweight/obese individuals.