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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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Probiotic intervention benefits multiple neural behaviors in older adults with mild cognitive impairment.
Fei, Y, Wang, R, Lu, J, Peng, S, Yang, S, Wang, Y, Zheng, K, Li, R, Lin, L, Li, M
Geriatric nursing (New York, N.Y.). 2023;51:167-175
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Mild cognitive impairment (MCI) is an intermediate stage between the normal cognitive changes associated with aging and dementia. Recent research shows that probiotic supplementation can regulate the balance of the intestinal flora and improve self-care ability and cognition in older adults. The aim of this study was to explore the effects and the underlying mechanisms of probiotic supplementation on MCI older adults. This study was a pilot randomised controlled trial (RCT) to investigate the effects of 12 weeks of probiotic supplementation in patients with MCI. Participants were randomly assigned to the probiotic group or control group. Results demonstrated the beneficial effects of probiotic supplementation intervention on multiple neural behaviours by regulating the homeostasis of the gut microbiota in older MCI patients. Authors conclude that this study provided new insights into nutrition interventions in older MCI patients. However, further trials with larger cohorts should be conducted to confirm the effects of probiotic intervention in MCI patients and provide more clinical evidence for its preventive and therapeutic effects.
Abstract
Probiotic supplements were shown to improve cognitive function in Alzheimer's disease (AD) patients. However, it is still unclear whether this applies to older individuals with mild cognitive impairment (MCI). We aimed to explore the effects of probiotic supplementation on multiple neural behaviors in older adults with MCI. Forty-two MCI patients (age > 60 years) were randomly divided into two groups and consumed either probiotics (n=21) or placebo (n=21) for 12 weeks. Various scale scores, gut microbiota measures and serological indicators were recorded pre- and posttreatment. After 12 weeks of intervention, cognitive function and sleep quality were improved in the probiotic group compared with those in the control group, and the underlying mechanisms were associated with changes in the intestinal microbiota. In conclusion, our study demonstrated that probiotic treatment enhanced cognitive function and sleep quality in older MCI patients, thus providing important insights into the clinical prevention and treatment of MCI.
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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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PRO-DEMET Randomized Controlled Trial on Probiotics in Depression-Pilot Study Results.
Gawlik-Kotelnicka, O, Margulska, A, Skowrońska, A, Strzelecki, D
Nutrients. 2023;15(6)
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Depression often coexists with metabolic abnormalities, and metabolic syndrome (MetS) is diagnosed in 30% of depressed subjects. Importantly, both obesity and MetS have been found to be independently associated with depressive symptoms and inflammation. The aim of this study was to investigate the effect of probiotics in the treatment of depressive disorders with possible comorbid MetS and its components. This study was an internal feasibility study based on the main randomised study - a single-centre, parallel-group, prospective, randomised, double-blind, placebo-controlled pilot trial. Adult patients (≥18 years) with depressive disorders were randomly assigned (1:1) into either the placebo or probiotic group. Results showed a positive association between probiotics supplementation and psychometric parameters together with the metabolic profile, serum inflammation markers, and biomarkers of metabolic-associated fatty liver disease in patients with depressive disorders. Authors conclude that the findings of their study would be suitable for determining the potential clinical use of probiotics and assessing certain key factors such as potential biomarkers of response.
Abstract
There is a pressing need to identify new treatment options for depression and its comorbidities. Depression often coexists with metabolic complications, and the two may share a pathophysiological overlap, including inflammation and microbiota changes. Microbiota interventions (e.g., probiotics) may represent a safe and easy-to-use treatment option as an adjunctive therapy in patients only partially responsive to pharmacologic treatment. (1) Objective: The paper presents the results of a feasibility and pilot study. The study is an internal part of a randomized controlled trail (RCT) of the effect of probiotic supplementation on psychometric, anthropometric, metabolic, and inflammatory parameters in adult patients with depressive disorders depending on the presence of metabolic syndrome. (2) Methods: The trial has a four-arm, parallel-group, prospective, randomized, double-blind, controlled design. Sixty participants received a probiotic preparation containing Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175 over 60 days. The feasibility of the study design was assessed, as well as the rates of recruitment, eligibility, consent, and study completion. The following were assessed: depressive, anxiety and stress symptoms, quality of life, blood pressure, body mass index and waist circumference, complete blood count with differential, serum levels of C-reactive protein, high-density lipoprotein cholesterol, triglycerides, fasting glucose, some secondary markers of inflammation and metabolic health, as well as noninvasive biomarkers of liver fibrosis (APRI and FIB-4). (3) Results: The study was found to be generally feasible. The eligibility rate was 52% of recruited participants with 80% completing the study protocol. No differences in sociodemographic or anthropometric factors or basic laboratory findings were found between the placebo and probiotic group at the start of the intervention period. Importantly, the proportion of recruited participants fulfilling the criteria of metabolic syndrome was too low. (4) Conclusions: Whilst the whole study protocol was feasible, some different timepoint procedures require modification. The major weakness of the recruitment methods was that the percentage of metabolic arms participants was insufficient. Overall, the full RCT design on probiotics in depression with vs. without metabolic syndrome was shown to be feasible with little modification.
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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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Modulating the Gut Microbiome in Multiple Sclerosis Management: A Systematic Review of Current Interventions.
Tsogka, A, Kitsos, DK, Stavrogianni, K, Giannopapas, V, Chasiotis, A, Christouli, N, Tsivgoulis, G, Tzartos, JS, Giannopoulos, S
Journal of clinical medicine. 2023;12(24)
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Multiple sclerosis (MS) is an autoimmune disease caused by the altered immune system mistakenly attacking the central nervous system. While genetics play a leading causative role in the manifestation of this disease, other contributing environmental factors can also exist, such as a disruption in the intestinal microbial composition. Previous research has shown that the bidirectional communication between the brain's and gut's health, also known as the gut-brain axis, may contribute to the prognosis of MS. Modulating gut microbial composition can be a therapeutic strategy in MS patients to manage symptoms and prevent disease progression. This systematic review assessed different protocols for modulating gut microbial composition, including dietary modifications, probiotic use, intermittent fasting, and faecal microbial transplantation. The review included thirteen studies that compared the effects of the above gut microbial modulation intervention protocols in MS patients with healthy participants. While different dietary modification strategies improved MS symptoms, probiotic supplementations and intermittent fasting reduced inflammation, and faecal microbial transplantation showed promising positive effects in a few reports. Due to the methodological limitations of the included studies, further robust studies are required to evaluate the beneficial effects of gut microbial modulation strategies in reducing the symptoms of MS patients. However, healthcare professionals can use the results of this study to understand the benefits of gut microbial modulation in MS patients.
Abstract
This review attempted to explore all recent clinical studies that have investigated the clinical and autoimmune impact of gut microbiota interventions in multiple sclerosis (MS), including dietary protocols, probiotics, fecal microbiota transplantation (FMT), and intermittent fasting (IF). Methods: Thirteen studies were held between 2011 and 2023 this demonstrated interventions in gut microbiome among patients with MS and their impact the clinical parameters of the disease. These included specialized dietary interventions, the supply of probiotic mixtures, FMT, and IF. Results: Dietary interventions positively affected various aspects of MS, including relapse rates, EDSS disability scores, MS-related fatigue, and metabolic features. Probiotic mixtures showed promising results on MS-related fatigue, EDSS parameters, inflammation; meanwhile, FMT-though a limited number of studies was included-indicated some clinical improvement in similar variables. IF showed reductions in EDSS scores and significant improvement in patients' emotional statuses. Conclusions: In dietary protocols, clinical MS parameters, including relapse rate, EDSS, MFIS, FSS, and MSQoL54 scales, were significantly improved through the application of a specific diet each time. Probiotic nutritional mixtures promote a shift in inflammation towards an anti-inflammatory cytokine profile in patients with MS. The administration of such mixtures affected disability, mood levels, and quality of life among patients with MS. FMT protocols possibly demonstrate a therapeutic effect in some case reports. IF protocols were found to ameliorate EDSS and FAMS scores. All interventional means of gut microbiome modulation provided significant conclusions on several clinical aspects of MS and highlight the complexity in the relationship between MS and the gut microbiome.
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Effect of Probiotic Bifidobacterium breve in Improving Cognitive Function and Preventing Brain Atrophy in Older Patients with Suspected Mild Cognitive Impairment: Results of a 24-Week Randomized, Double-Blind, Placebo-Controlled Trial.
Asaoka, D, Xiao, J, Takeda, T, Yanagisawa, N, Yamazaki, T, Matsubara, Y, Sugiyama, H, Endo, N, Higa, M, Kasanuki, K, et al
Journal of Alzheimer's disease : JAD. 2022;88(1):75-95
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Probiotics are “live microorganisms which when administered in adequate amounts, confer a health benefit on the host” as defined by the International Scientific Association for Probiotics and Prebiotics. The aim of this study was to assess the effect of the probiotic strain Bifidobacterium breve MCC1274 in enhancing cognition and preventing brain atrophy of older patients with mild cognitive impairment (MCI). This study is a double-blind, randomised placebo-controlled trial. Participants (n=130) were randomly assigned to one of the two groups: probiotic group or placebo group. Results show improvement of cognitive function on some subscales scores but not the total scores by the consumption of B. breve MCC1274 in the MCI subjects. In addition, the probiotic supplementation for 24 weeks suppressed brain atrophy progression based on brain MRI. Authors conclude that B. breve MCC1274 is a practical approach for preventing cognitive impairment of MCI subjects. However, further research is necessary to understand B. breve MCC1274 mechanism(s) of action.
Abstract
BACKGROUND Probiotics have been reported to ameliorate cognitive impairment. OBJECTIVE We investigated the effect of the probiotic strain Bifidobacterium breve MCC1274 (A1) in enhancing cognition and preventing brain atrophy of older patients with mild cognitive impairment (MCI). METHODS In this RCT, 130 patients aged from 65 to 88 years old with suspected MCI received once daily either probiotic (B. breve MCC1274, 2×1010 CFU) or placebo for 24 weeks. Cognitive functions were assessed by ADAS-Jcog and MMSE tests. Participants underwent MRI to determine brain atrophy changes using Voxel-based Specific Regional Analysis System for Alzheimer's disease (VSRAD). Fecal samples were collected for the analysis of gut microbiota composition. RESULTS Analysis was performed on 115 participants as the full analysis set (probiotic 55, placebo 60). ADAS-Jcog subscale "orientation" was significantly improved compared to placebo at 24 weeks. MMSE subscales "orientation in time" and "writing" were significantly improved compared to placebo in the lower baseline MMSE (< 25) subgroup at 24 weeks. VSRAD scores worsened in the placebo group; probiotic supplementation tended to suppress the progression, in particular among those subjects with progressed brain atrophy (VOI Z-score ≥1.0). There were no marked changes in the overall composition of the gut microbiota by the probiotic supplementation. CONCLUSION Improvement of cognitive function was observed on some subscales scores only likely due to the lower sensitiveness of these tests for MCI subjects. Probiotics consumption for 24 weeks suppressed brain atrophy progression, suggesting that B. breve MCC1274 helps prevent cognitive impairment of MCI subjects.
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Probiotic Bifidobacterium longum BB68S Improves Cognitive Functions in Healthy Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial.
Shi, S, Zhang, Q, Sang, Y, Ge, S, Wang, Q, Wang, R, He, J
Nutrients. 2022;15(1)
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Probiotics, live microorganisms that provide health benefits when administered regularly in the host, substantially affect the composition as well as metabolic output of the gut microbiome. Probiotics can impact brain health and host behaviours through the microbiota-gut-brain axis. The aim of this study was to investigate the effects of Bifidobacterium longum BB68S (BB68S) [probiotics] on the cognitive function of healthy elderly people aged 60–75 years. This study was a randomised, double-blind, placebo-controlled trial. The subjects (n=60) were evenly and randomly allocated to the probiotic or placebo groups. Results showed that the subjects had good tolerance to the probiotic intervention in this study and no side effects were reported. The BB68S intervention significantly improved cognitive function compared to that of controls. Amongst the 12 items, list learning, story memory, figure copy, line orientation, coding, story recall, and figure recall scores of the probiotic group improved significantly. Among the 5 domains, only language did not significantly improve. Authors conclude that BB68S could improve cognitive function thus probiotics may be used as an alternative strategy to advance cognitive aging and promote healthy aging.
Abstract
Probiotics could improve cognitive functions in patients with neurological disorders such as Alzheimer’s disease, but the effects on cognitive function in healthy older adults without cognitive impairment need further study. The purpose of this study was to investigate the effect of Bifidobacterium longum BB68S (BB68S) on cognitive functions among healthy older adults without cognitive impairment. A randomized, double-blind, placebo-controlled trial was conducted with 60 healthy older adults without cognitive impairment who were divided into probiotic or placebo groups and required to consume either a sachet of probiotic (BB68S, 5 × 1010 CFU/sachet) or placebo once daily for 8 weeks. The Montreal Cognitive Assessment (MoCA) was used as an inclusion screening tool to screen elderly participants with healthy cognitive function in our study, and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognitive function in subjects before and after intervention as an assessment tool. BB68S significantly improved subjects’ cognitive functions (total RBANS score increased by 18.89 points after intervention, p < 0.0001), especially immediate memory, visuospatial/constructional, attention, and delayed memory domains. BB68S intervention increased the relative abundances of beneficial bacteria Lachnospira, Bifidobacterium, Dorea, and Cellulosilyticum, while decreasing those of bacteria related to cognition impairment, such as Collinsella, Parabacteroides, Tyzzerella, Bilophila, unclassified_c_Negativicutes, Epulopiscium, Porphyromonas, and Granulicatella. In conclusion, BB68S could improve cognitive functions in healthy elderly adults without cognitive impairment, along with having beneficial regulatory effects on their gut microbiota. This study supports probiotics as a strategy to promote healthy aging and advances cognitive aging research.
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Clinical, gut microbial and neural effects of a probiotic add-on therapy in depressed patients: a randomized controlled trial.
Schaub, AC, Schneider, E, Vazquez-Castellanos, JF, Schweinfurth, N, Kettelhack, C, Doll, JPK, Yamanbaeva, G, Mählmann, L, Brand, S, Beglinger, C, et al
Translational psychiatry. 2022;12(1):227
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Major depressive disorder (MDD) is one of the most prevalent and burdensome psychiatric disorders. Compelling preclinical data indicate that the gut microbiota affects brain functions and depressive behaviour, providing a promising novel target for the treatment of depression. The aims of this study were to (i) examine the effect of a short-term, high-dose probiotic add-on therapy on depressive symptoms in MDD patients, and (ii) explore the effects of a probiotic supplementation on gut microbiota composition as well as brain structure and function. This study was a double-blind randomised controlled trial of a probiotic add-on therapy for four weeks in depressed patients. Patients (n=60) were randomly allocated to the two study groups and tested at three different time points. Results showed that an add-on probiotic treatment improves depressive symptoms and maintains healthy enterotypes, species richness and increases specific health related bacterial taxa. Furthermore, on a neural level, probiotics altered negative biases and emotional valence additionally to treatment-as-usual for depression. Authors conclude that their findings highlight the role of the microbiota-gut-brain axis in MDD and emphasises the potential of microbiota-related treatment approaches as therapies to improve the effectiveness of current treatments in depression.
Abstract
A promising new treatment approach for major depressive disorder (MDD) targets the microbiota-gut-brain (MGB) axis, which is linked to physiological and behavioral functions affected in MDD. This is the first randomized controlled trial to determine whether short-term, high-dose probiotic supplementation reduces depressive symptoms along with gut microbial and neural changes in depressed patients. Patients with current depressive episodes took either a multi-strain probiotic supplement or placebo over 31 days additionally to treatment-as-usual. Assessments took place before, immediately after and again four weeks after the intervention. The Hamilton Depression Rating Sale (HAM-D) was assessed as primary outcome. Quantitative microbiome profiling and neuroimaging was used to detect changes along the MGB axis. In the sample that completed the intervention (probiotics N = 21, placebo N = 26), HAM-D scores decreased over time and interactions between time and group indicated a stronger decrease in the probiotics relative to the placebo group. Probiotics maintained microbial diversity and increased the abundance of the genus Lactobacillus, indicating the effectivity of the probiotics to increase specific taxa. The increase of the Lactobacillus was associated with decreased depressive symptoms in the probiotics group. Finally, putamen activation in response to neutral faces was significantly decreased after the probiotic intervention. Our data imply that an add-on probiotic treatment ameliorates depressive symptoms (HAM-D) along with changes in the gut microbiota and brain, which highlights the role of the MGB axis in MDD and emphasizes the potential of microbiota-related treatment approaches as accessible, pragmatic, and non-stigmatizing therapies in MDD. Trial Registration: www.clinicaltrials.gov , identifier: NCT02957591.
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Effects of Lactiplantibacillus plantarum OLL2712 on Memory Function in Older Adults with Declining Memory: A Randomized Placebo-Controlled Trial.
Sakurai, K, Toshimitsu, T, Okada, E, Anzai, S, Shiraishi, I, Inamura, N, Kobayashi, S, Sashihara, T, Hisatsune, T
Nutrients. 2022;14(20)
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On the Alzheimer’s disease spectrum, which is the most common cause of dementia, the typical symptom at onset is impaired memory. As the disease progresses, other cognitive domains, such as language, visuospatial cognition, and executive function, are impaired, gradually making it impossible to maintain independence in daily life. The aim of this study was to test the protective effects of 12 weeks of supplementation with heat-treated Lactiplantibacillus OLL2712 cells on memory function in older adults. This study was a double-blind placebo-controlled trial in which participants were randomly assigned to the active or placebo group. Results showed that OLL2712 consumption had a protective effect on memory function in older adults. However, there was no significant effect of OLL2712 intake on verbal memory in either of the analyses. Furthermore, in the gut microbiota analysis, the bacterial composition of the active group showed significantly lower abundance ratios of bacterial species linked to inflammation (Lachnoclostridium, Monoglobus, and Oscillibacter). Authors conclude that continuous intake of OLL2712 may be an effective approach to protect memory function in older adults.
Abstract
The use of probiotics is expected to be an intervention in neurodegenerative conditions that cause dementia owing to their ability to modulate neuroinflammatory responses via the microbiome-gut-brain axis. Therefore, we selected Lactiplantibacillus plantarum OLL2712 (OLL2712), the optimal anti-inflammatory lactic acid bacteria strain with high IL-10-inducing activity in immune cells, and aimed to verify its protective effects on memory function in older adults. A 12-week, randomized, double-blind, placebo-controlled trial was performed with older adults over the age of 65 years with declining memory. The participants consumed either powder containing heat-treated OLL2712 cells or placebo. Memory function was assessed using a computer-assisted cognitive test, Cognitrax. Daily dietary nutrient intake was assessed using the Brief-type Self-administered Diet History Questionnaire (BDHQ). The composition of the gut microbiota was analyzed by fecal DNA extraction and 16S rDNA sequencing. Data from 78 participants who completed the entire procedure were analyzed, and significant improvements in composite memory and visual memory scores were observed in the active group, after accounting for the effect of daily nutritional intake (p = 0.044 and p = 0.021, respectively). In addition, the active group had a lower abundance ratio of Lachnoclostridium, Monoglobus, and Oscillibacter genera, which have been reported to be involved in inflammation. The present study suggests that OLL2712 ingestion has protective effects against memory function decline in older adults.