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Probiotic, prebiotic, synbiotic and fermented food supplementation in psychiatric disorders: A systematic review of clinical trials.
Ribera, C, Sánchez-Ortí, JV, Clarke, G, Marx, W, Mörkl, S, Balanzá-Martínez, V
Neuroscience and biobehavioral reviews. 2024;:105561
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Abstract
The use of probiotics, prebiotics, synbiotics or fermented foods can modulate the gut-brain axis and constitute a potentially therapeutic intervention in psychiatric disorders. This systematic review aims to identify current evidence regarding these interventions in the treatment of patients with DSM/ICD psychiatric diagnoses. Forty-seven articles from 42 studies met the inclusion criteria. Risk of bias was assessed in all included studies. Major depression was the most studied disorder (n = 19 studies). Studies frequently focused on schizophrenia (n = 11) and bipolar disorder (n = 5) and there were limited studies in anorexia nervosa (n = 4), ADHD (n = 3), Tourette (n = 1), insomnia (n = 1), PTSD (n = 1) and generalized anxiety disorder (n = 1). Except in MDD, current evidence does not clarify the role of probiotics and prebiotics in the treatment of mental illness. Several studies point to an improvement in the immune and inflammatory profile (e.g. CRP, IL6), which may be a relevant mechanism of action of the therapeutic response identified in these studies. Future research should consider lifestyle and dietary habits of patients as possible confounders that may influence inter-individual treatment response.
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Microbes, oxytocin and stress: Converging players regulating eating behavior.
Cuesta-Marti, C, Uhlig, F, Muguerza, B, Hyland, N, Clarke, G, Schellekens, H
Journal of neuroendocrinology. 2023;(9):e13243
Abstract
Oxytocin is a peptide-hormone extensively studied for its multifaceted biological functions and has recently gained attention for its role in eating behavior, through its action as an anorexigenic neuropeptide. Moreover, the gut microbiota is involved in oxytocinergic signaling through the brain-gut axis, specifically in the regulation of social behavior. The gut microbiota is also implicated in appetite regulation and is postulated to play a role in central regulation of hedonic eating. In this review, we provide an overview on oxytocin and its individual links with the microbiome, the homeostatic and non-homeostatic regulation of eating behavior as well as social behavior and stress.
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Impact of dietary fiber on gut microbiota composition, function and gut-brain-modules in healthy adults - a systematic review protocol.
Lachmansingh, DA, Valderrama, B, Bastiaanssen, T, Cryan, J, Clarke, G, Lavelle, A
HRB open research. 2023;:62
Abstract
BACKGROUND The gut microbiota has been extensively implicated in health and disease. The functional outputs of the gut microbiota, such as microbial metabolites, are considered particularly important in this regard. Significant associations exist between alterations in the relative abundance of specific microbial taxa and mental health disorders. Dietary fiber has the potential to alter gut microbiota composition and function, modifying bacterial enzymatic function and the production of metabolites. As many taxa of microorganisms have enzymes capable of producing or degrading neurochemicals i.e. neuroactive gut brain modules, new predictive tools can be applied to existing datasets such as those harvested from dietary fiber interventions. We endeavor to perform a systematic review in order to identify studies reporting compositional gut microbiota alterations after interventions with dietary fiber in healthy individuals. We aim to also extract from the selected studies publicly available microbial genomic sequence datasets for reanalysis with a consistent bioinformatics pipeline, with the ultimate intention of identifying altered gut brain modules following dietary fiber interventions. METHODS Interventional trials and randomized controlled studies that are originally published, including cross-over and non-crossover design and involving healthy adult humans will be included. A systematic search of PubMed/MEDLINE and EMBASE, two electronic databases, will be completed. DISCUSSION Various types of dietary fiber have an impact on the gut microbiota composition, with some promoting the growth of particular taxa while others are reduced in relative abundance. Our search focuses on the impact of this food component on the microbiota of healthy individuals. Compositional gut microbial changes have been reported and our review will compile and update these observations after reanalysis of their datasets with a consistent bioinformatic pipeline. From this it may be possible to predict more detailed functional consequences in terms of neuroactive gut brain modules, of the compositional alterations in gut microbial taxa.
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Microbiota-immune-brain interactions: A lifespan perspective.
Ratsika, A, Cruz Pereira, JS, Lynch, CMK, Clarke, G, Cryan, JF
Current opinion in neurobiology. 2023;:102652
Abstract
There is growing appreciation of key roles of the gut microbiota in maintaining homeostasis and influencing brain and behaviour at critical windows across the lifespan. Mounting evidence suggests that communication between the gut and the brain could be the key to understanding multiple neuropsychiatric disorders, with the immune system coming to the forefront as an important mechanistic mediator. Throughout the lifespan, the immune system exchanges continuous reciprocal signals with the central nervous system. Intestinal microbial cues alter immune mediators with consequences for host neurophysiology and behaviour. Several factors challenge the gut microbiota composition, which in response release molecules with neuro- and immuno-active potential that are crucial for adequate neuro-immune interactions. In this review, multiple factors contributing to the upkeep of the fine balance between health and disease of these systems are discussed, and we elucidate the potential mechanistic implications for the gut microbiota inputs on host brain and behaviour across the lifespan.
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Inflammation, Lifestyle Factors, and the Microbiome-Gut-Brain Axis: Relevance to Depression and Antidepressant Action.
Donoso, F, Cryan, JF, Olavarría-Ramírez, L, Nolan, YM, Clarke, G
Clinical pharmacology and therapeutics. 2023;(2):246-259
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Abstract
Depression is considered a major public health concern, where existing pharmacological treatments are not equally effective across all patients. The pathogenesis of depression involves the interaction of complex biological components, such as the immune system and the microbiota-gut-brain axis. Adjunctive lifestyle-oriented approaches for depression, including physical exercise and special diets are promising therapeutic options when combined with traditional antidepressants. However, the mechanisms of action of these strategies are incompletely understood. Accumulating evidence suggests that physical exercise and specific dietary regimens can modulate both the immune system and gut microbiota composition. Here, we review the current information about the strategies to alleviate depression and their crosstalk with both inflammatory mechanisms and the gut microbiome. We further discuss the role of the microbiota-gut-brain axis as a possible mediator for the adjunctive therapies for depression through inflammatory mechanisms. Finally, we review existing and future adjunctive strategies to manipulate the gut microbiota with potential use for depression, including physical exercise, dietary interventions, prebiotics/probiotics, and fecal microbiota transplantation.
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Feed your microbes to deal with stress: a psychobiotic diet impacts microbial stability and perceived stress in a healthy adult population.
Berding, K, Bastiaanssen, TFS, Moloney, GM, Boscaini, S, Strain, CR, Anesi, A, Long-Smith, C, Mattivi, F, Stanton, C, Clarke, G, et al
Molecular psychiatry. 2022
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Plain language summary
Psychobiotic describe any exogenous intervention that leads to a bacterially mediated impact on the brain. Probiotics and prebiotics have shown promising results as psychobiotic agents in both animal and human studies. The aim of this study was to investigate the potential of a whole diet psychobiotic approach to modulate the microbiota composition and function, affect responses to and feelings of stress and improve mood in a healthy population. This study is a single-blind, randomized, controlled study which recruited healthy adult (male and female) participants with poor dietary habits, aged 18–59 years. Participants were block randomized (block of 4, stratified by gender) into either intervention or control group using randomly permuted blocks and were instructed to follow their respective diet for 4 weeks. Results show that a short term psychobiotic dietary intervention improved perceived stress in a healthy population, while eliciting specific metabolic changes in the gut microbiota. Authors conclude that underlying microbial influences need to be investigated and future preclinical experiments are required to explore causality and decipher mechanistic pathways.
Expert Review
Conflicts of interest:
None
Take Home Message:
Eating foods known to have a positive influence on gut microbial composition could elicit benefits in terms of reducing perceived stress and improving sleep quality.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
This RCT explored the impact of a psychobiotic diet, compared to a control diet, on perceived stress, sleep and gut microbiota.
A high psychobiotic diet is one high in prebiotic and fermented foods. In this study, a psychobiotic diet included daily recommended consumption and servings of the following:
- High prebiotic fruit & veg (6-8)
- Grains (5-8)
- Fermented foods (2-3)
- Legumes (3-4 per week)
Methodology:
- A single-blind, randomised, controlled study
- 45 healthy adults (18-59 years) with poor dietary habits
- Sample size determined by previous microbiome research - target not reached due to introduction of covid restrictrictions
- Active intervention (n=24) received dietitian advice to follow psychobitoic diet
- Control intervention (n=21) received dietitian advice largely based on the Irish Healthy Eating Guidelines food pyramid
- Intervention duration 4 weeks.
- Assessed on questionnaire measures of perceived stress and sleep, pre and post-intervention (no primary outcome defined)
- Shotgun microbiome analysis on stool samples, pre and post-intervention
Results:
- Perceived stress improved in the psychobiotic diet group
- Subjective sleep quality improved in the psychobiotic diet group
- Only subtle changes in microbial composition and function
- More stable microbiota throughout the study (regardless of diet) was correlated with greater changes in perceived stress
- Neither cortisol awakening response nor measured immune markers were affected by dietary intervention
Conclusions:
- Using a diet targeted to positively modulate gut-brain communication may have the potential for reducing stress and improving sleep
- Although improvements in stress were only observed for the intervention group – the post-intervention stress levels were not significantly different between the groups.
- Thus, we should interpret the results with some caution
Clinical practice applications:
- Providing advice on dietary intake of foods known to positively impact gut microbiota may be helpful for individuals affected by stress or sleep problems
- The inclusion of the following foods may be helpful:
- High prebiotic fruit & veg (6-8 per day)
- Grains (5-8 per day)
- Fermented foods (2-3 per day)
- Legumes (3-4 per week)
Considerations for future research:
- Important to replicate these results in a larger sample
- It might be helpful to investigate individual aspects of the diet separately, to assess their individual impact
- Objective measures of sleep (such as actigraphy recordings) might provide additionally useful findings
- It would be interesting to explore the effect of the psychobiotic diet in other conditions
- Chronobiology or chrononutrition - i.e. looking at timing of the foods proposed in the section above
Abstract
The impact of diet on the microbiota composition and the role of diet in supporting optimal mental health have received much attention in the last decade. However, whether whole dietary approaches can exert psychobiotic effects is largely understudied. Thus, we investigated the influence of a psychobiotic diet (high in prebiotic and fermented foods) on the microbial profile and function as well as on mental health outcomes in a healthy human population. Forty-five adults were randomized into either a psychobiotic (n = 24) or control (n = 21) diet for 4 weeks. Fecal microbiota composition and function was characterized using shotgun sequencing. Stress, overall health and diet were assessed using validated questionnaires. Metabolic profiling of plasma, urine and fecal samples was performed. Intervention with a psychobiotic diet resulted in reductions of perceived stress (32% in diet vs. 17% in control group), but not between groups. Similarly, biological marker of stress were not affected. Additionally, higher adherence to the diet resulted in stronger decreases in perceived stress. While the dietary intervention elicited only subtle changes in microbial composition and function, significant changes in the level of 40 specific fecal lipids and urinary tryptophan metabolites were observed. Lastly, microbial volatility was linked to greater changes in perceived stress scores in those on the psychobiotic diet. These results highlight that dietary approaches can be used to reduce perceived stress in a human cohort. Using microbiota-targeted diets to positively modulate gut-brain communication holds possibilities for the reduction of stress and stress-associated disorders, but additional research is warranted to investigate underlying mechanisms, including the role of the microbiota.
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Diet and the microbiota - gut - brain-axis: a primer for clinical nutrition.
Ribeiro, G, Ferri, A, Clarke, G, Cryan, JF
Current opinion in clinical nutrition and metabolic care. 2022;(6):443-450
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Abstract
PURPOSE OF REVIEW Diet is an essential modulator of the microbiota - gut - brain communication in health and disease. Consequently, diet-induced microbiome states can impact brain health and behaviour. The integration of microbiome into clinical nutrition perspectives of brain health is sparse. This review will thus focus on emerging evidence of microbiome-targeted dietary approaches with the potential to improve brain disorders. RECENT FINDINGS Research in this field is evolving toward randomized controlled trials using dietary interventions with the potential to modulate pathways of the microbiota - gut - brain-axis. Although most studies included small cohorts, the beneficial effects of Mediterranean-like diets on symptoms of depression or fermented foods on the immune function of healthy individuals shed light on how this research line can grow. With a clinical nutrition lens, we highlight several methodological limitations and knowledge gaps, including the quality of dietary intake information, the design of dietary interventions, and missing behavioural outcomes. SUMMARY Findings in diet - microbiome - brain studies can have groundbreaking implications in clinical nutrition practice and research. Modulating brain processes through diet via the gut microbiota raises numerous possibilities. Novel dietary interventions targeting the microbiota - gut - brain-axis can offer various options to prevent and treat health problems such as mental disorders. Furthermore, knowledge in this field will improve current nutritional guidelines for disease prevention.
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Exercise and Creatine Supplementation to Augment the Adaptation of Exercise Training Among Breast Cancer Survivors Completing Chemotherapy: Protocol for an Open-label Randomized Controlled Trial (the THRIVE Study).
Patel, DI, Gonzalez, A, Moon, C, Serra, M, Bridges, PB, Hughes, D, Clarke, G, Kilpela, L, Jiwani, R, Musi, N
JMIR research protocols. 2022;(4):e26827
Abstract
BACKGROUND In breast cancer survivors, chemotherapy-induced muscle loss has been shown to be attenuated with structured resistance exercise. Creatine supplementation can increase bioenergetics in skeletal muscle, which helps to improve overall strength and endurance and reduce muscular fatigue. Therefore, we hypothesize that adding creatinine supplementation to exercise training will accelerate improvements in strength, endurance, and bioenergetics in breast cancer survivors. OBJECTIVE The primary objective is to determine the effects of combining creatine supplementation with exercise on modulating strength and physical function in breast cancer survivors by comparing these effects to those of exercise alone. The secondary objectives are to determine if creatine supplementation and exercise can increase the intramuscular storage of creatine and improve body composition by comparing this intervention to exercise alone. METHODS We aim to test our hypothesis by conducting an open-label randomized controlled trial of 30 breast cancer survivors who have completed chemotherapy within 6 months of enrollment. Eligible participants will be equally randomized (1:1) to either a creatine and exercise group or an exercise-only group for this 12-week intervention. Individuals who are randomized to receive creatine will be initially dosed at 20 g per day for 7 days to boost the availability of creatine systemically. Thereafter, the dose will be reduced to 5 g per day for maintenance throughout the duration of the 12-week protocol. All participants will engage in 3 center-based exercise sessions, which will involve completing 3 sets of 8 to 12 repetitions on chest press, leg press, seated row, shoulder press, leg extension, and leg curl machines. The primary outcomes will include changes in strength, body composition, and physical function in breast cancer survivors. The secondary outcomes will be intramuscular concentrations of creatine and adenosine triphosphate in the vastus lateralis, midthigh cross-sectional area, and quality of life. RESULTS As of October 2021, a total of 9 patients have been enrolled into the study. No unexpected adverse events have been reported. CONCLUSIONS Creatine is being studied as a potential agent for improving strength, endurance, and bioenergetics in breast cancer survivors following chemotherapy. The findings from our trial may have future implications for supporting breast cancer survivors in reversing the muscle loss experienced during chemotherapy and improving their physical function and quality of life. TRIAL REGISTRATION ClinicalTrials.gov NCT04207359; https://clinicaltrials.gov/ct2/show/NCT04207359. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/26827.
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Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome: A multicenter retrospective study.
Berens, S, Dong, Y, Fritz, N, Walstab, J, D'Amato, M, Zheng, T, Wahl, V, Boekstegers, F, Bermejo, JL, Martinez, C, et al
World journal of gastroenterology. 2022;(21):2334-2349
Abstract
BACKGROUND Single-nucleotide polymorphisms (SNPs) of the serotonin type 3 receptor subunit (HTR3) genes have been associated with psychosomatic symptoms, but it is not clear whether these associations exist in irritable bowel syndrome (IBS). AIM: To assess the association of HTR3 polymorphisms with depressive, anxiety, and somatization symptoms in individuals with IBS. METHODS In this retrospective study, 623 participants with IBS were recruited from five specialty centers in Germany, Sweden, the United States, the United Kingdom, and Ireland. Depressive, anxiety, and somatization symptoms and sociodemographic characteristics were collected. Four functional SNPs - HTR3A c.-42C>T, HTR3B c.386A>C, HTR3C c.489C>A, and HTR3E c.*76G>A - were genotyped and analyzed using the dominant and recessive models. We also performed separate analyses for sex and IBS subtypes. SNP scores were calculated as the number of minor alleles of the SNPs above. The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays. RESULTS Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model (F depressive = 7.475, P depressive = 0.006; F anxiety = 6.535, P anxiety = 0.011). A higher SNP score (range 0-6) was linked to a worsened depressive symptoms score (F = 7.710, P-linear trend = 0.006) in IBS. The potential relevance of the HTR3C SNP was corroborated, showing changes in the expression level of 5-HT3AC variant receptors. CONCLUSION We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS. The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.
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Short chain fatty acids: Microbial metabolites for gut-brain axis signalling.
O'Riordan, KJ, Collins, MK, Moloney, GM, Knox, EG, Aburto, MR, Fülling, C, Morley, SJ, Clarke, G, Schellekens, H, Cryan, JF
Molecular and cellular endocrinology. 2022;:111572
Abstract
The role of the intestinal microbiota as a regulator of gut-brain axis signalling has risen to prominence in recent years. Understanding the relationship between the gut microbiota, the metabolites it produces, and the brain will be critical for the subsequent development of new therapeutic approaches, including the identification of novel psychobiotics. A key focus in this regard have been the short-chain fatty acids (SCFAs) produced by bacterial fermentation of dietary fibre, which include butyrate, acetate, and propionate. Ongoing research is focused on the entry of SCFAs into systemic circulation from the gut lumen, their migration to cerebral circulation and across the blood brain barrier, and their potential to exert acute and chronic effects on brain structure and function. This review aims to discuss our current mechanistic understanding of the direct and indirect influence that SCFAs have on brain function, behaviour and physiology, which will inform future microbiota-targeted interventions for brain disorders.