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Effect of gut microbiome modulation on muscle function and cognition: the PROMOTe randomised controlled trial.
Ni Lochlainn, M, Bowyer, RCE, Moll, JM, García, MP, Wadge, S, Baleanu, AF, Nessa, A, Sheedy, A, Akdag, G, Hart, D, et al
Nature communications. 2024;15(1):1859
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Humans lose skeletal muscle with advancing age, and this can progress to sarcopenia. Dietary protein is crucial for maintaining skeletal muscle health; however, several factors can lead to reduced protein intake in older age. The aim of this study was to test whether the addition of gut microbiome modulation could augment established muscle function improvements from combined protein (branched chain amino acids [BCAA]) and resistance exercise. This study was based on the PROMOTe (effect of PRebiotic and prOtein on Muscle in Older Twins) trial which was a randomised controlled trial in which twin pairs (n= 72) were randomised, one twin to each study arm. Results showed that prebiotics improved cognition but did not impact muscle strength and function, compared with placebo. Furthermore, gut microbiome modulation via prebiotic supplementation in the context of ageing-muscle research is feasible and well tolerated, with clear responses noted in the gut microbiota composition and function. Authors concluded that cheap and readily available gut microbiome interventions hold promise for improving cognitive frailty in our ageing population.
Abstract
Studies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut microbiota may play a role in both anabolic resistance of older muscle, and cognition. In this placebo controlled double blinded randomised controlled trial of 36 twin pairs (72 individuals), aged ≥60, each twin pair are block randomised to receive either placebo or prebiotic daily for 12 weeks. Resistance exercise and branched chain amino acid (BCAA) supplementation is prescribed to all participants. Outcomes are physical function and cognition. The trial is carried out remotely using video visits, online questionnaires and cognitive testing, and posting of equipment and biological samples. The prebiotic supplement is well tolerated and results in a changed gut microbiome [e.g., increased relative Bifidobacterium abundance]. There is no significant difference between prebiotic and placebo for the primary outcome of chair rise time (β = 0.579; 95% CI -1.080-2.239 p = 0.494). The prebiotic improves cognition (factor score versus placebo (β = -0.482; 95% CI,-0.813, -0.141; p = 0.014)). Our results demonstrate that cheap and readily available gut microbiome interventions may improve cognition in our ageing population. We illustrate the feasibility of remotely delivered trials for older people, which could reduce under-representation of older people in clinical trials. ClinicalTrials.gov registration: NCT04309292.
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Effect of prebiotics, probiotics, synbiotics on depression: results from a meta-analysis.
Zhang, Q, Chen, B, Zhang, J, Dong, J, Ma, J, Zhang, Y, Jin, K, Lu, J
BMC psychiatry. 2023;23(1):477
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Major depressive disorder (MDD) is a mood disorder that impairs psychosocial function and quality of life. Recent studies show that prebiotics, probiotics, and synbiotics reveal a novel way to treat psychiatric disorders such as depression through the microbiota-gut-brain axis. The aim of this study was to evaluate the effectiveness of prebiotics, probiotics and synbiotics in alleviating depressive symptoms. This study was a meta-analysis of thirteen studies with a total of 786 participants who were allocated to the intervention group (n=427) and the placebo group (n=359). Results showed that the overall effects of probiotics, prebiotics and synbiotics on depressive symptoms were significantly superior to those of placebo. Additionally, biological sex was a vital factor that influenced patients’ responses to the treatment. Authors concluded that agents that manipulate gut microbiota might become a novel approach to treat patients with mild-to-moderate depression.
Abstract
Accumulating studies have shown the effects of gut microbiota management tools in improving depression. We conducted a meta-analysis to evaluate the effects of prebiotics, probiotics, and synbiotics on patients with depression. We searched six databases up to July 2022. In total, 13 randomized controlled trials (RCTs) with 786 participants were included. The overall results demonstrated that patients who received prebiotics, probiotics or synbiotics had significantly improved symptoms of depression compared with those in the placebo group. However, subgroup analysis only confirmed the significant antidepressant effects of agents that contained probiotics. In addition, patients with mild or moderate depression could both benefit from the treatment. Studies with a lower proportion of females reported stronger effects for alleviating depressive symptoms. In conclusion, agents that manipulate gut microbiota might improve mild-to-moderate depression. It is necessary to further investigate the benefits of prebiotic, probiotic and synbiotic treatments relative to antidepressants and follow up with individuals over a longer time before these therapies are implemented in clinical practice.
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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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Wild blueberry (poly)phenols can improve vascular function and cognitive performance in healthy older individuals: a double-blind randomized controlled trial.
Wood, E, Hein, S, Mesnage, R, Fernandes, F, Abhayaratne, N, Xu, Y, Zhang, Z, Bell, L, Williams, C, Rodriguez-Mateos, A
The American journal of clinical nutrition. 2023;117(6):1306-1319
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The risk of developing both cardiovascular and neurodegenerative diseases increases with aging. Growing evidence from epidemiological and human intervention trials indicates that (poly)phenols may have cardioprotective properties as well as the ability to improve cognitive function. The aim of this study was to investigate the effects of daily wild blueberry (WBB) (poly)phenol consumption on vascular function and cognitive performance in healthy older individuals. This study was a randomised, double-blinded, placebo-controlled parallel design study. A total of 61 healthy older individuals were recruited and randomly assigned to one of the two arms; placebo intervention or blueberry intervention group. Results showed that long-term consumption of a dietary achievable amount of WBB enhanced vascular and cognitive function in older adults. Authors conclude that gut microbiota and vascular blood flow may play important roles in mediating the cognitive benefits shown by the consumption of (poly)phenol-rich foods.
Abstract
BACKGROUND Evidence suggests that the intake of blueberry (poly)phenols is associated with improvements in vascular function and cognitive performance. Whether these cognitive effects are linked to increases in cerebral and vascular blood flow or changes in the gut microbiota is currently unknown. METHODS A double-blind, parallel randomized controlled trial was conducted in 61 healthy older individuals aged 65-80 y. Participants received either 26 g of freeze-dried wild blueberry (WBB) powder (302 mg anthocyanins) or a matched placebo (0 mg anthocyanins). Endothelial function measured by flow-mediated dilation (FMD), cognitive function, arterial stiffness, blood pressure (BP), cerebral blood flow (CBF), gut microbiome, and blood parameters were measured at baseline and 12 wk following daily consumption. Plasma and urinary (poly)phenol metabolites were analyzed using microelution solid-phase extraction coupled with liquid chromatography-mass spectrometry. RESULTS A significant increase in FMD and reduction in 24 h ambulatory systolic BP were found in the WBB group compared with the placebo group (0.86%; 95% CI: 0.56, 1.17, P < 0.001; -3.59 mmHg; 95% CI: -6.95, -0.23, P = 0.037; respectively). Enhanced immediate recall on the auditory verbal learning task, alongside better accuracy on a task-switch task was also found following WBB treatment compared with placebo (P < 0.05). Total 24 h urinary (poly)phenol excretion increased significantly in the WBB group compared with placebo. No changes in the CBF or gut microbiota composition were found. CONCLUSIONS Daily intake of WBB powder, equivalent to 178 g fresh weight, improves vascular and cognitive function and decreases 24 h ambulatory systolic BP in healthy older individuals. This suggests that WBB (poly)phenols may reduce future CVD risk in an older population and may improve episodic memory processes and executive functioning in older adults at risk for cognitive decline. Clinical Trial Registration number in clinicaltrials.gov: NCT04084457.
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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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Intake of Lactiplantibacillus plantarum HEAL9 Improves Cognition in Moderately Stressed Subjects: A Randomized Controlled Study.
Önning, G, Montelius, C, Hillman, M, Larsson, N
Nutrients. 2023;15(15)
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It is thought that there is a bidirectional communication pathway between the gut microbiota and the brain, known as the gut-brain axis. Stress, anxiety and low mood and the hormones produced when experiencing these have been shown to be improved by the introduction of healthy gut microbiota through probiotic use. As such, the use of probiotics may be of benefit to mental health problems. This randomised control trial of 129 individuals with moderate stress aimed to determine the effect of one probiotic strain Lactoplantibacillus plantarum HEAL9 (LPHEAL9) on the gut-brain axis. The results showed that following supplementation for 12 weeks, cognitive function was significantly improved compared to placebo and there was an improvement in the feelings of confusion, anger, and depression. There was a trend for improved sleep for individuals given LPHEAL9, however this was not significantly better than individuals given placebo. There were no benefits to perceived stress following LPHEAL9 supplementation. It was concluded that LPHEAL9 improved cognitive function compared to placebo and this may be due to improved mood and sleep. This study could be used by healthcare professionals to specifically recommend LPHEAL9 to individuals with stress, anxiety, and low mood.
Abstract
BACKGROUND The usage of probiotics has expanded beyond the areas of gut and immune health improvement. Several studies have shown the positive impact associated between probiotics and stress, cognition, and mood; a relationship referred to as the gut-brain axis. METHOD The aim of this exploratory study was to evaluate the effect of the probiotic strain Lactiplantibacillus plantarum HEAL9 (LPHEAL9) on the gut-brain axis in subjects with moderate stress. One hundred and twenty-nine subjects aged 21-52 years completed the study, randomized to consume either LPHEAL9 (n = 65) or placebo (n = 64) for 12 weeks. RESULTS Perceived stress and awakening cortisol were significantly reduced over time in both groups. A significant improvement in four cognition tests after consumption of LPHEAL9 compared to placebo was observed (rapid information processing test, numeric working memory test, paired associated learning, and word recall, p < 0.05). There was a tendency for a significantly better improvement in the LPHEAL9 group for three mood subscales (Confusion-Bewilderment, Anger-Hostility, and Depression-Dejection) and for fewer subjects with poor sleep in the LPHEAL9 group compared to placebo (p < 0.10). CONCLUSIONS Intake of LPHEAL9 significantly improved cognitive functions compared to the placebo, potentially by ameliorating aspects of mood and sleep.
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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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A Randomized, Double-Blind, Placebo-Controlled Study of an Anthocyanin-Rich Functional Ingredient on Cognitive Function and Eye Dryness in Late Adulthood Volunteers: Roles of Epigenetic and Gut Microbiome Modulations.
Wattanathorn, J, Tong-Un, T, Thukham-Mee, W, Paholpak, P, Rangseekhajee, P
Nutrients. 2023;15(16)
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The global market of functional foods targeting wellness promotion, disease risk reduction, and quality of life promotion has been increasing. Due to this demand, the development of novel functional ingredients is essential when producing new fortified foods and beverages. The aim of this study was to determine the effect of the eight-week consumption of a functional soup containing “Anthaplex” [a novel functional ingredient consisting of the extracts of purple waxy corn (Zea mays) and coloured sticky rice (Oryza sativa)] on cognitive function and eye dryness in healthy volunteers in late adulthood. This study was an 8-week, 3-arm, randomised, double-blind, placebo-controlled study. A total of 69 participants were randomly assigned to placebo, D2 (2g of Anthaplex), or D4 (4g of Anthaplex) treatment group. Results showed that “Anthaplex” can improve cognitive function and working memory together with eye dryness. Authors concluded that “Anthaplex” could be a new functional ingredient for supplements aiming to improve cognitive function and eye dryness.
Abstract
Due to the rising demand for supplements targeting cognitive enhancement and dry eye together with the health benefits of anthocyanins, we have developed a functional soup containing an anthocyanin-rich functional ingredient, or "Anthaplex," and assessed the effects on cognitive function and eye dryness together with the possible mechanisms. A total of 69 male and female health volunteers were randomized and divided into placebo, D2, and D4 groups. All subjects consumed 120 mL of placebo or functional soup containing "Anthaplex" either at 2 or 4 g per serving per day within 5 min in the morning for eight weeks. The cognitive function, working memory, dry eye, AChE, MAO, MAO-A, MAO-B, and GABA-T activities, BDNF, HAC, HDAC, and DNMT activities, pH, and amount of lactic acid-producing bacteria, particularly Lactobacillus and Bifidobacterium spp. in feces, were determined before intervention and after eight weeks of consumption. Subjects who consumed the "Anthaplex" soup had improved cognitive function, working memory, eye dryness, histone acetylation, ACh E suppression, and BDNF with increased Bifidobacterium spp. but decreased pH in feces. These data suggest that "Anthaplex" improves cognitive function and eye dryness via the modulations of the histone acetylation process, gut microbiome, and cholinergic function.
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Effect of short-term, high-dose probiotic supplementation on cognition, related brain functions and BDNF in patients with depression: a secondary analysis of a randomized controlled trial.
Schneider, E, Doll, JPK, Schweinfurth, N, Kettelhack, C, Schaub, AC, Yamanbaeva, G, Varghese, N, Mählmann, L, Brand, S, Eckert, A, et al
Journal of psychiatry & neuroscience : JPN. 2023;48(1):E23-E33
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Major depressive disorder (MDD) is often thought of as being solely a mood disorder. However, several studies have shown that sufferers can also experience decreased brain function such as memory loss and poor attention. Current therapies for MDD focus on the balancing of mood and leaves the problem of reduced brain function unattended. The gut microbiota has recently been shown to influence brain function and altered gut microbiota composition has been seen in individuals with MDD. Targeting the gut microbiota may therefore represent a novel target for MDD treatments. This secondary analysis of a randomised control trial aimed to determine whether a probiotic multistrain supplement could improve brain function in 60 individuals with depression. The results showed that probiotics improved the brain function in two different ways, the immediate recall of words, and the improvement of decreased neural function in the hippocampal part of the brain, which has been associated with MDD. It was concluded that probiotic supplementation can enhance verbal episodic memory and improve neural function associated with impaired brain function in MDD. This study could be used by healthcare professionals to understand that the health of the gut microbiota can have an influence on brain function and that probiotics may help individuals with MDD who are suffering from poorer memory.
Abstract
BACKGROUND In major depressive disorder (MDD), cognitive dysfunctions strongly contribute to functional impairments but are barely addressed in current therapies. Novel treatment strategies addressing cognitive symptoms in depression are needed. As the gut microbiota-brain axis is linked to depression and cognition, we investigated the effect of a 4-week high-dose probiotic supplementation on cognitive symptoms in depression. METHODS This randomized controlled trial included 60 patients with MDD, of whom 43 entered modified intention-to-treat analysis. A probiotic supplement or indistinguishable placebo containing maltose was administered over 31 days in addition to treatment as usual for depression. Participant scores on the Verbal Learning Memory Test (VLMT), Corsi Block Tapping Test, and both Trail Making Test versions as well as brain-derived neurotrophic factor levels were assessed at 3 different time points: before, immediately after and 4 weeks after intervention. Additionally, brain activation changes during working memory processing were investigated before and immediately after intervention. RESULTS We found a significantly improved immediate recall in the VLMT in the probiotic group immediately after intervention, and a trend for a time × group interaction considering all time points. Furthermore, we found a time × group interaction in hippocampus activation during working memory processing, revealing a remediated hippocampus function in the probiotic group. Other measures did not reveal significant changes. LIMITATIONS The modest sample size resulting from our exclusion of low-compliant cases should be considered. CONCLUSION Additional probiotic supplementation enhances verbal episodic memory and affects neural mechanisms underlying impaired cognition in MDD. The present findings support the importance of the gut microbiota-brain axis in MDD and emphasize the potential of microbiota-related regimens to treat cognitive symptoms in depression. CLINICAL TRIAL REGISTRATION clinicaltrials.gov identifier NCT02957591.