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Psychobiotic Lactobacillus plantarum JYLP-326 relieves anxiety, depression, and insomnia symptoms in test anxious college via modulating the gut microbiota and its metabolism.
Zhu, R, Fang, Y, Li, H, Liu, Y, Wei, J, Zhang, S, Wang, L, Fan, R, Wang, L, Li, S, et al
Frontiers in immunology. 2023;14:1158137
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Test anxiety, characterised by feelings of failure, tension, and worrying when an individual faces a vital test for promoting, occurs prevalently among college students. Lactobacillus plantarum, has become increasingly popular in reducing the severity of anxiety and depression in stressed animal models. The main aim of this study was to evaluate the psychological effects of Lactobacillus plantarum JYLP-326 (JYLP-326) on exam stress-induced behaviours like anxiety, depression, and insomnia. This study enrolled 60 anxious and 30 un-anxious undergraduates preparing for the approaching exams. Out of the 60 anxious participants, 30 were selected randomly to receive the probiotic product and the other 30 received a placebo product. The 30 un-anxious students were assigned as the healthy control group. Results demonstrated that the intervention of JYLP-326 is effective in alleviating exam stress-induced symptoms in college students. Furthermore, it also protected against exam stress-induced dysbiosis of the gut microbiota and the disturbances of faecal metabolomic. Authors conclude that the changed gut microbiota genera and faecal metabolites were closely associated with stress-related symptoms like anxiety/depression and insomnia, indicating that they might be regarded as biomarkers for diagnosing and treating stress and anxiety disorders.
Abstract
INTRODUCTION Test anxiety is a common issue among college students, which can affect their physical and psychological health. However, effective interventions or therapeutic strategies are still lacking. This study aims to evaluate the potential effects of Lactobacillus plantarum JYLP-326 on test anxious college students. METHODS Sixty anxious students were enrolled and randomly allocated to the placebo group and the probiotic group. Both groups were instructed to take placebo and JYLP-326 products twice per day for three weeks, respectively. Thirty unanxious students with no treatments were assigned to a regular control group. The anxiety, depression, and insomnia questionnaires were used to measure students' mental states at the baseline and the end of this study. 16S rRNA sequencing and untargeted metabolomics were performed to analyze the changes in the gut microbiota and fecal metabolism. RESULTS The questionnaire results suggested that JYLP-326 administration could relieve the symptoms of anxiety, depression, and insomnia in test anxious students. The gut microbiomes of the placebo group showed a significantly greater diversity index than the control group (p < 0.05). An increased abundance of Bacteroides and Roseburia at the genus level was observed in the placebo group, and the relative abundance of Prevotella and Bifidobacterium decreased. Whereas, JYLP-326 administration could partly restore the disturbed gut microbiota. Additionally, test anxiety was correlated with disordered fecal metabolomics such as a higher Ethyl sulfate and a lower Cyclohexylamine, which could be reversed after taking JYLP-326. Furthermore, the changed microbiota and fecal metabolites were significantly associated with anxiety-related symptoms. CONCLUSION The results indicate that the intervention of L. plantarum JYLP-326 could be an effective strategy to alleviate anxiety, depression, and insomnia in test anxious college students. The potential mechanism underlying this effect could be related to the regulation of gut microbiota and fecal metabolites.
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Bifidobacterium longum subsp. longum Reduces Perceived Psychological Stress in Healthy Adults: An Exploratory Clinical Trial.
Boehme, M, Rémond-Derbez, N, Lerond, C, Lavalle, L, Keddani, S, Steinmann, M, Rytz, A, Dalile, B, Verbeke, K, Van Oudenhove, L, et al
Nutrients. 2023;15(14)
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Psychosocial stress is a common issue and one way in which nutrition may modulate the stress response is via the microbiota-gut-brain axis. This 6-week randomised, double-blind, placebo-controlled trial of 45 healthy adults with mild-to-moderate stress evaluated the effects of Bifidobacterium longum (BL) NCC3001 on psychological and physiological markers of stress and the response to an acute stress test. Outcome measures included cortisol awakening response, heart rate, heart rate variability and various questionnaires assessing stress, anxiety, depression, sleep and gastrointestinal symptoms. Compared to placebo, probiotic intake led to a significant decrease in perceived stress and an improvement in subjective sleep after 6 weeks. There was no difference in cortisol awakening response. The subjects in both groups did not experience significant gastrointestinal symptoms and scored low on anxiety and depression at baseline. In response to the acute stress test, cortisol levels were higher in the probiotic than the placebo group, whilst no clear differences were seen in heart rate and heart rate variability. Subjects in the probiotic group had a lower pain experience during the stress test whilst subjects in the placebo group had an increase in positive mood following the test. The authors conclude that these results support their hypothesis that BL NCC3001 may alleviate stress and improve sleep in adults with moderate stress levels.
Expert Review
Conflicts of interest:
None
Take Home Message:
- There is mounting evidence to suggest that nutritional interventions can influence our stress responses. One of the routes by which nutrition can influence physiological and psychological stress responses involves the microbiota– gut–brain-axis.
- This exploratory trial suggests that supplementation with Bifidobacterium longum (BL) strain NCC3001 leads to a beneficial effect on stress relief and improves subjective sleep quality in a healthy adult population reporting moderate levels of psychological stress.
Evidence Category:
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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:
Introduction
A randomised, placebo-controlled, two-arm, parallel, double-blind exploratory clinical trial was conducted to investigate the effect Bifidobacterium longum (BL) strain NCC3001 on stress-related psychological and physiological parameters and acute stress in healthy adults who typically experience mild-to-moderate-levels of stress.
Method
47 Participants between the ages of 25-65 years old with mild-to-moderate psychological stress received 1x1010 CFU of Bifidobacterium longum (BL) strain NCC3001 daily or a placebo for 6 weeks.
Participants completed the Perceived Stress Scale (PSS), the Hospital Anxiety and Depression Scales (HAD-A and HADS-D), the Gastrointestinal Symptom Rating Scale (GSRA), the Pittsburgh Sleep Quality Index (PSQI) questionnaire, the Positive and Negative Affect Schedule (PANAS), the State Trait Anxiety Inventory (STAI-6), the Maastricht Acute Stress Test (MAST) and the Visual Analog Scales (VAS, which measures pain intensity) during the clinical study. The Depression, Anxiety and Stress Scale (DASS-42) questionnaire was also used to depict the progression of the participants through the study.
Faecal samples were taken at baseline and 6 weeks and awakening saliva samples were taken at baseline, 2, 4, 6 and 8 weeks. At the endpoint, 45/49 (91%) of the subjects completed the study. One participant reported an adverse event and the other withdrew without an explanation. Two participants were excluded from the full analysis.
Results
The primary outcomes were:
- After 6-week of the probiotic intervention, there was a significant decrease in perceived stress in the probiotic group (21.4%) compared to the placebo group (-10.2%), p = 0.017.
- There was a significant improvement in subjective sleep in the probiotic group compared to the placebo group (p = 0.037).
- There was a significant decrease in the positive PANAS change score from the pre-stressor stage in the probiotic group compared to the placebo group (p = 0.01).
- There were lower pain values (VAS) scores from pre-stressor to post-stressor in the probiotic group compared to the placebo group (p = 0.05).
- There was no significant difference between groups in anxiety (HADS-A) and Depression (HADS_D) scores.
Conclusion
Oral supplementation with BL NCC3001 may have beneficial effects on stress relief and improves subjective sleep quality in a healthy adult population reporting moderate levels of psychological stress.
Clinical practice applications:
- While the mechanism underlying the correlation between the microbiota and the gut-brain-axis is not fully understood, it is thought to play a critical role in the links between the microbiota, mood, stress, and brain health.
- This exploratory trial additionally supports the potential of specific probiotics being used to reduce perceived stress and improve subjective sleep quality in healthy adults.
Considerations for future research:
- Larger, powered clinical trials are needed to provide further insights into the mechanisms underlying the stress-relieving and sleep-improving effect of Bifidobacterium longum.
- Furthermore, the dosage and duration of the probiotics need further investigation in a larger healthy population.
- Comparative research is needed to help investigate the effect of different probiotic strains on stress relief and sleep quality.
Abstract
Emerging science shows that probiotic intake may impact stress and mental health. We investigated the effect of a 6-week intervention with Bifidobacterium longum (BL) NCC3001 (1 × 1010 CFU/daily) on stress-related psychological and physiological parameters in 45 healthy adults with mild-to-moderate stress using a randomized, placebo-controlled, two-arm, parallel, double-blind design. The main results showed that supplementation with the probiotic significantly reduced the perceived stress and improved the subjective sleep quality score compared to placebo. Comparing the two groups, momentary subjective assessments concomitant to the Maastricht Acute Stress Test revealed a lower amount of pain experience in the probiotic group and a higher amount of relief at the end of the procedure in the placebo group, reflected by higher scores in the positive affect state. The awakening of the salivary cortisol response was not affected by the intervention, yet the reduction observed in the salivary cortisol stress response post-intervention was higher in the placebo group than the probiotic group. Multivariate analysis further indicated that a reduction in perceived stress correlated with a reduction in anxiety, in depression, and in the cortisol awakening response after the 6-week intervention. This exploratory trial provides promising insights into BL NCC3001 to reduce perceived stress in a healthy population and supports the potential of nutritional solutions including probiotics to improve mental health.
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Psychobiotic Effects on Anxiety Are Modulated by Lifestyle Behaviors: A Randomized Placebo-Controlled Trial on Healthy Adults.
Morales-Torres, R, Carrasco-Gubernatis, C, Grasso-Cladera, A, Cosmelli, D, Parada, FJ, Palacios-García, I
Nutrients. 2023;15(7)
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The microbiota-gut-brain axis refers to the complex communication system between the human gastrointestinal tract, the micro-organisms which inhabit it, and the peripheral and central nervous systems. In recent years, human trials have linked the microbiome with specific processes that are expected to contribute to well-being. The aim of this study was to assess the effect of a psychobiotic formulation specifically on well-being, exploring the extent to which these effects might be modulated by lifestyle factors such as diet, physical activity, social connectedness, and others. This study was a four week, double-blind, randomised, placebo-controlled trial. Participants were randomised into one of two groups; placebo or probiotic group. Results showed that there were no significant effects of probiotics on a set of psychological measures of well-being. However, further analysis revealed that healthy lifestyle behaviours were significantly correlated with wellbeing across scales. Authors conclude that their findings demonstrate the need of controlling lifestyle variables as a standard practice in human microbiome research and mental health research in general.
Abstract
Psychobiotics are modulators of the Microbiota-Gut-Brain Axis (MGBA) with promising benefits to mental health. Lifestyle behaviors are established modulators of both mental health and the MGBA. This randomized placebo-controlled clinical trial (NCT04823533) on healthy adults (N = 135) tested 4 weeks of probiotic supplementation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175). We assessed effects on wellbeing, quality of life, emotional regulation, anxiety, mindfulness and interoceptive awareness. We then analyzed if lifestyle behaviors modulated probiotic effectiveness. Results showed no significant effects of probiotic intake in whole sample outcomes. Correlational analyses revealed Healthy Behaviors were significantly correlated with wellbeing across scales. Moreover, the linear mixed-effects model showed that the interaction between high scores in Healthy Behaviors and probiotic intake was the single significant predictor of positive effects on anxiety, emotional regulation, and mindfulness in post-treatment outcomes. These findings highlight the relevance of controlling for lifestyle behaviors in psychobiotic and mental health research.
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Effects of Microbiota Imbalance in Anxiety and Eating Disorders: Probiotics as Novel Therapeutic Approaches.
Navarro-Tapia, E, Almeida-Toledano, L, Sebastiani, G, Serra-Delgado, M, García-Algar, Ó, Andreu-Fernández, V
International journal of molecular sciences. 2021;22(5)
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The interest in mental health has increased recently. Anxiety and mood disorders are associated with many disabilities and there is a close relationship between eating disorders and anxiety. Although current medical treatments for anxiety disorders are safer than a few decades ago; the effectiveness in some of them has not improved, they have side effects and can cause addiction. Therefore, the development of new tools to restore mental health without the undesired effects is necessary. Recent studies indicate that patients with generalized anxiety or eating disorders (anorexia nervosa, bulimia nervosa, and binge-eating disorders) show a specific gut microbiota profile, and this imbalance can be partially restored after a single or multi-strain probiotic supplementation. The purpose of this review is to look at the main microbial patterns seen in patients with generalized anxiety and/or eating disorders as well as the importance of probiotics as a preventive or a therapeutic tool in these pathologies. The studies reviewed showed an imbalance of microbial communities in patients with anxiety and with eating disorders. The effect of probiotics in reducing anxiety seems to be more effective the higher the baseline anxiety level of the individual. For eating disorders, the correction of dysbiosis may be associated with the physical and emotional well-being of these subjects. Further study of the intestinal microbiota will enable progress in the study of therapeutic approaches of these areas.
Abstract
Anxiety and eating disorders produce a physiological imbalance that triggers alterations in the abundance and composition of gut microbiota. Moreover, the gut-brain axis can be altered by several factors such as diet, lifestyle, infections, and antibiotic treatment. Diet alterations generate gut dysbiosis, which affects immune system responses, inflammation mechanisms, the intestinal permeability, as well as the production of short chain fatty acids and neurotransmitters by gut microbiota, which are essential to the correct function of neurological processes. Recent studies indicated that patients with generalized anxiety or eating disorders (anorexia nervosa, bulimia nervosa, and binge-eating disorders) show a specific profile of gut microbiota, and this imbalance can be partially restored after a single or multi-strain probiotic supplementation. Following the PRISMA methodology, the current review addresses the main microbial signatures observed in patients with generalized anxiety and/or eating disorders as well as the importance of probiotics as a preventive or a therapeutic tool in these pathologies.
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Probiotic Supplementation Improves Cognitive Function and Mood with Changes in Gut Microbiota in Community-Dwelling Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.
Kim, CS, Cha, L, Sim, M, Jung, S, Chun, WY, Baik, HW, Shin, DM
The journals of gerontology. Series A, Biological sciences and medical sciences. 2021;76(1):32-40
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Aging is characterized by progressive decline in biological functions of the organism. Diet is one of the critical lifestyle factors for physical and mental well-being throughout the life span, including later life. The aim of this study was to investigate the effects of probiotics consumption on intestinal and brain health in elders over the age of 65. This study is a randomised, double-blind, placebo-controlled, multicentre trial. All participants, study coordinators, and researchers were blinded throughout the entire study. Sixty-three participants were randomized, with 31 and 32 subjects in the placebo and probiotics group, respectively. Results demonstrate that probiotics have system-wide effects on the gut–brain axis in healthy community-dwelling older adults by promoting cognitive and mental health and changing the gut microbial composition. Authors conclude that their findings provide evidence that probiotics have health-promoting properties as part of a healthy diet in the general population of independently living older adults.
Abstract
Probiotics have been proposed to ameliorate cognitive impairment and depressive disorder via the gut-brain axis in patients and experimental animal models. However, the beneficial role of probiotics in brain functions of healthy older adults remains unclear. Therefore, a randomized, double-blind, and placebo-controlled multicenter trial was conducted to determine the effects of probiotics on cognition and mood in community-dwelling older adults. Sixty-three healthy elders (≥65 years) consumed either placebo or probiotics containing Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI for 12 weeks. The gut microbiota was analyzed using 16S rRNA sequencing and bioinformatics. Brain functions were measured using the Consortium to Establish a Registry for Alzheimer's disease, Satisfaction with life scale, stress questionnaire, Geriatric depression scale, and Positive affect and negative affect schedule. Blood brain-derived neurotrophic factor (BDNF) was determined using enzyme-linked immunosorbent assay. Relative abundance of inflammation-causing gut bacteria was significantly reduced at Week 12 in the probiotics group (p < .05). The probiotics group showed greater improvement in mental flexibility test and stress score than the placebo group (p < .05). Contrary to placebo, probiotics significantly increased serum BDNF level (p < .05). Notably, the gut microbes significantly shifted by probiotics (Eubacterium and Clostridiales) showed significant negative correlation with serum BDNF level only in the probiotics group (RS = -0.37, RS = -0.39, p < .05). In conclusion, probiotics promote mental flexibility and alleviate stress in healthy older adults, along with causing changes in gut microbiota. These results provide evidence supporting health-promoting properties of probiotics as a part of healthy diet in the older adults.
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Gut feelings: A randomised, triple-blind, placebo-controlled trial of probiotics for depressive symptoms.
Chahwan, B, Kwan, S, Isik, A, van Hemert, S, Burke, C, Roberts, L
Journal of affective disorders. 2019;253:317-326
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Depression is a debilitating psychiatric disorder that is the leading cause of disability world-wide. Multiple causes of depression have been identified, including genetic, neurological, inflammatory, personality, cognitive, and environmental factors. The aim of this study was to investigate the effectiveness of the multispecies probiotic Ecologic® Barrier for reducing symptoms in adults with mild to severe levels of depression. The study was a triple-blinded parallel, placebo-controlled randomised clinical trial. Participants were randomly allocated into two groups; probiotic and placebo. 71 participants with depressive symptoms were recruited and allocated sequentially over 12 months. Results indicate that all participants across both probiotic and placebo groups exhibited a reduction in depressive symptoms over the time-period of the trial. Thus, the routine involved with daily preparation and consumption of the probiotic and scheduled appointments, as well as involvement in these behaviours with the aim of seeking improvement in depressive symptoms had positive impacts on mood, irrespective of whether the probiotic or placebo was consumed. Authors conclude that their findings offer evidence to indicate that probiotic consumption can exert change on cognitive patterns associated with depression.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This study offers evidence to indicate that probiotic consumption can exert change on cognitive patterns associated with depression.
- The study suggests that probiotics, rather than having a direct effect on depressive symptoms, potentially act on immune system activity, inflammation and gut barrier integrity which contribute to the expression of depression.
- Probiotics may be a useful adjunct to potentiate the effects of other therapies, such as CBT.
- This study points to the validity of managing physical health as part of mental health treatment.
Evidence Category:
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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:
With evidence suggesting that decreased gut barrier function and inflammation are correlated with depression, this study set out to determine the effect of consumption of probiotic supplements on depressive symptoms from a sample of 71 participants with depression. The study was a triple-blinded parallel, placebo-controlled randomised clinical trial conducted over 8 weeks in Australia. Pre and post intervention measures of symptoms and vulnerability markers of depression as well as gut microbiota were compared alongside psychological variables and gut microbiota composition to non-depressed, placebo and probiotic groups. All the clinical trial participants demonstrated an improvement in symptoms – participants in the probiotic group demonstrated a significantly greater reduction in cognitive reactivity compared with the placebo group. Probiotics did not significantly alter the microbiota of depressed individuals, however a significant correlation was found between Ruminococcus gnavus and one of the metrics for depression.
Clinical practice applications:
This study was small and carried out over a short period of time. While significant results were found, which signify potential considerations for clinical practice, the results from this study do not offer evidence that the probiotics used had a direct effect on depressive symptoms – they suggest that probiotics potentially act on cognitive processes contributing to depression which may include immune system activity, inflammation, and gut barrier integrity. Overall, this study offers evidence to indicate that probiotic consumption can exert change on cognitive patterns associated with depression. In clinical practice, probiotics may be a useful adjunct to potentiate the effects of therapies, such as CBT. Finally, the use of probiotics promotes the concept of managing physical health as part of mental health treatment.
Considerations for future research:
These preliminary results are promising and offer a number of future research and clinical avenues to build upon. The results do however, indicate that a longer trial may be needed to fully assess the effects of probiotics on mood and the mechanisms by which probiotics may be influencing this. The study also suggests that further research using a range of concentrations in a dose response study may be warranted to determine the optimal dose; a greater dose over a longer period may produce detectable changes in microbiota as well as further differences in psychological data.
Abstract
BACKGROUND Depression is the leading cause of disability worldwide; with evidence suggesting that decreased gut barrier function and inflammation are correlated with depressive symptoms. We conducted a clinical trial to determine the effect of consumption of probiotic supplements (Winclove's Ecologic® Barrier) on depressive symptoms in a sample of participants with mild to severe depression. METHOD 71 participants were randomly allocated to either probiotic or placebo, which was, consumed daily over eight weeks. Pre- and post-intervention measures of symptoms and vulnerability markers of depression as well as gut microbiota composition were compared. Clinical trial participants were also compared on psychological variables and gut microbiota composition to a non-depressed group (n = 20). RESULTS All clinical trial participants demonstrated improvement in symptoms, suggesting non-specific therapeutic effects associated with weekly monitoring visits. Participants in the probiotic group demonstrated a significantly greater reduction in cognitive reactivity compared with the placebo group, particularly in the mild/moderate subgroup. Probiotics did not significantly alter the microbiota of depressed individuals, however, a significant correlation was found between Ruminococcus gnavus and one depression metric. LIMITATIONS There was a high attrition rate, which may be attributed to weekly monitoring visits. Additionally, modulation of the gut microbiota may need more specific testing to distinguish subtle changes. CONCLUSIONS While microbiota composition was similar between all groups, probiotics did affect a psychological variable associated with susceptibility to depression. Further research is needed to investigate how probiotics can be utilised to modify mental wellbeing, and whether they can act as an adjunct to existing treatments.