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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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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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Stress matters: Randomized controlled trial on the effect of probiotics on neurocognition.
Papalini, S, Michels, F, Kohn, N, Wegman, J, van Hemert, S, Roelofs, K, Arias-Vasquez, A, Aarts, E
Neurobiology of stress. 2019;10:100141
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Increasing animal studies indicate the role of probiotics in regulating mood and cognition through the gut-brain axis, however in human studies evidence of this causal association is lacking. The aim of this double-blind, randomised, placebo-controlled intervention was to investigate the effects of probiotics on neurocognitive measures in 58 healthy participants. Participants were randomly assigned to either probiotic or placebo group and were tested once before and after the 28-day intervention. The neurocognitive outcomes measured included emotion reactivity, emotion regulation, cognitive control and the effects of acute stress on working memory. These were assessed through functional MRI (fMRI) and questionnaires. This study found when stress was induced, probiotic supplementation led to a significant improvement in working memory performance. Without stress, there was no causal association between neurocognitive outcomes and probiotic intake. Based on these results, the authors conclude that during challenging situations, probiotics can aid in buffering the detrimental effects of stress on cognition.
Abstract
Probiotics are microorganisms that provide health benefits when consumed. In animals, probiotics reverse gut microbiome-related alterations in depression-like symptoms, in cognition, and in hormonal stress response. However, in humans, a causal understanding of the gut-brain link in emotion and cognition is lacking. Additionally, whether the effects of probiotics on neurocognition are visible only in presence of stress, remains unclear. We investigated the effects of a multispecies probiotic (Ecologic®Barrier) on specific neurocognitive measures of emotion reactivity, emotion regulation, and cognitive control using fMRI. Critically, we also tested whether probiotics can buffer against the detrimental effects of acute stress on working memory. In a double blind, randomized, placebo-controlled, between-subjects intervention study, 58 healthy participants were tested once before and once after a 28-day intervention. Without stress induction, probiotics did not affect brain, behavioral, or related self-report measures. However, relative to placebo, the probiotics group did show a significant stress-related increase in working memory performance after supplementation. This change was associated with intervention-related neural changes in frontal cortex during cognitive control exclusively in the probiotics group. Overall, our results show neurocognitive effects of a multispecies probiotic in healthy women only under challenging situations, buffering against the detrimental effects of stress on cognition.
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Reversal of cognitive decline: a novel therapeutic program.
Bredesen, DE
Aging. 2014;6(9):707-17
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Alzheimer’s Disease (AD) is estimated to affect 30 million individuals globally, with projections as high as 150 million by 2050 if no effective treatment is found. This report describes a personalised, multi-modal, therapeutic programme used with 10 individuals with various degrees of cognitive decline. The goal was to optimise metabolic parameters and lifestyle factors and was personalised based on laboratory test results. 9 out of 10 of the case study patients experienced improvement in cognitive abilities, beginning within 3-6 months of starting the programme. These effects were sustained at 2.5 year follow up. The 1 patient who did not benefit had advanced AD, in comparison to the other patients with subjective or mild cognitive decline. The authors call for a more extensive trial of the therapeutic programme.
Abstract
This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system.