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1.
Potential of dietary polyphenols for protection from age-related decline and neurodegeneration: a role for gut microbiota?
Ross, FC, Mayer, DE, Horn, J, Cryan, JF, Del Rio, D, Randolph, E, Gill, CIR, Gupta, A, Ross, RP, Stanton, C, et al
Nutritional neuroscience. 2024;:1-19
Abstract
Many epidemiological studies have shown the beneficial effects of a largely plant-based diet, and the strong association between the consumption of a Mediterranean-type diet with healthy aging including a lower risk of cognitive decline. The Mediterranean diet is characterized by a high intake of olive oil, fruits and vegetables and is rich in dietary fiber and polyphenols - both of which have been postulated to act as important mediators of these benefits. Polyphenols are large molecules produced by plants to protect them from environmental threats and injury. When ingested by humans, as little as 5% of these molecules are absorbed in the small intestine with the majority metabolized by the gut microbiota into absorbable simple phenolic compounds. Flavan-3-ols, a type of flavonoid, contained in grapes, berries, pome fruits, tea, and cocoa have been associated with many beneficial effects on several risk factors for cardiovascular disease, cognitive function and brain regions involved in memory formation. Both preclinical and clinical studies suggest that these brain and heart benefits can be attributed to endothelial vascular effects and anti-inflammatory properties among others. More recently the gut microbiota has emerged as a potential modulator of the aging brain and intriguingly polyphenols have been shown to alter microbiota composition and be metabolized by different microbial species. However, there is a need for well controlled studies in large populations to identify predictors of response, particularly given the vast inter-individual variation of human gut microbiota.
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Fermented foods: Harnessing their potential to modulate the microbiota-gut-brain axis for mental health.
Balasubramanian, R, Schneider, E, Gunnigle, E, Cotter, PD, Cryan, JF
Neuroscience and biobehavioral reviews. 2024;:105562
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Abstract
Over the past two decades, whole food supplementation strategies have been leveraged to target mental health. In addition, there has been increasing attention on the ability of gut microbes, so called psychobiotics, to positively impact behaviour though the microbiota-gut-brain axis. Fermented foods offer themselves as a combined whole food microbiota modulating intervention. Indeed, they contain potentially beneficial microbes, microbial metabolites and other bioactives, which are being harnessed to target the microbiota-gut-brain axis for positive benefits. This review highlights the diverse nature of fermented foods in terms of the raw materials used and type of fermentation employed, and summarises their potential to shape composition of the gut microbiota, the gut to brain communication pathways including the immune system and, ultimately, modulate the microbiota-gut-brain axis. Throughout, we identify knowledge gaps and challenges faced in designing human studies for investigating the mental health-promoting potential of individual fermented foods or components thereof. Importantly, we also suggest solutions that can advance understanding of the therapeutic merit of fermented foods to modulate the microbiota-gut-brain axis.
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Existing and Future Strategies to Manipulate the Gut Microbiota With Diet as a Potential Adjuvant Treatment for Psychiatric Disorders.
Ross, FC, Mayer, DE, Gupta, A, Gill, CIR, Del Rio, D, Cryan, JF, Lavelle, A, Ross, RP, Stanton, C, Mayer, EA
Biological psychiatry. 2024;(4):348-360
Abstract
Nutrition and diet quality play key roles in preventing and slowing cognitive decline and have been linked to multiple brain disorders. This review compiles available evidence from preclinical studies and clinical trials on the impact of nutrition and interventions regarding major psychiatric conditions and some neurological disorders. We emphasize the potential role of diet-related microbiome alterations in these effects and highlight commonalities between various brain disorders related to the microbiome. Despite numerous studies shedding light on these findings, there are still gaps in our understanding due to the limited availability of definitive human trial data firmly establishing a causal link between a specific diet and microbially mediated brain functions and symptoms. The positive impact of certain diets on the microbiome and cognitive function is frequently ascribed with the anti-inflammatory effects of certain microbial metabolites or a reduction of proinflammatory microbial products. We also critically review recent research on pro- and prebiotics and nondietary interventions, particularly fecal microbiota transplantation. The recent focus on diet in relation to brain disorders could lead to improved treatment outcomes with combined dietary, pharmacological, and behavioral interventions.
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Fiber intake and fiber intervention in depression and anxiety: a systematic review and meta-analysis of observational studies and randomized controlled trials.
Aslam, H, Lotfaliany, M, So, D, Berding, K, Berk, M, Rocks, T, Hockey, M, Jacka, FN, Marx, W, Cryan, JF, et al
Nutrition reviews. 2023
Abstract
CONTEXT Dietary fibers hold potential to influence depressive and anxiety outcomes by modulating the microbiota-gut-brain axis, which is increasingly recognized as an underlying factor in mental health maintenance. OBJECTIVE Evidence for the effects of fibers on depressive and anxiety outcomes remains unclear. To this end, a systematic literature review and a meta-analysis were conducted that included observational studies and randomized controlled trials (RCTs). DATA SOURCES The PubMed, Embase, CENTRAL, CINAHL, and PsychINFO databases were searched for eligible studies. DATA EXTRACTION Study screening and risk-of-bias assessment were conducted by 2 independent reviewers. DATA ANALYSIS Meta-analyses via random effects models were performed to examine the (1) association between fiber intake and depressive and anxiety outcomes in observational studies, and (2) effect of fiber intervention on depressive and anxiety outcomes compared with placebo in RCTs. A total of 181 405 participants were included in 23 observational studies. In cross-sectional studies, an inverse association was observed between fiber intake and depressive (Cohen's d effect size [d]: -0.11; 95% confidence interval [CI]: -0.16, -0.05) and anxiety (d = -0.25; 95%CI, -0.38, -0.12) outcomes. In longitudinal studies, there was an inverse association between fiber intake and depressive outcomes (d = -0.07; 95%CI, -0.11, -0.04). In total, 740 participants were included in 10 RCTs, all of whom used fiber supplements. Of note, only 1 RCT included individuals with a clinical diagnosis of depression. No difference was found between fiber supplementation and placebo for depressive (d = -0.47; 95%CI, -1.26, 0.31) or anxiety (d = -0.30; 95%CI, -0.67, 0.07) outcomes. CONCLUSION Although observational data suggest a potential benefit for higher fiber intake for depressive and anxiety outcomes, evidence from current RCTs does not support fiber supplementation for improving depressive or anxiety outcomes. More research, including RCTs in clinical populations and using a broad range of fibers, is needed. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42021274898.
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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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Microbiota-Gut-Brain Axis Regulation of Adult Hippocampal Neurogenesis.
Guzzetta, KE, Cryan, JF, O'Leary, OF
Brain plasticity (Amsterdam, Netherlands). 2022;(1):97-119
Abstract
The birth, maturation, and integration of new neurons in the adult hippocampus regulates specific learning and memory processes, responses to stress, and antidepressant treatment efficacy. This process of adult hippocampal neurogenesis is sensitive to environmental stimuli, including peripheral signals from certain cytokines, hormones, and metabolites, which can promote or hinder the production and survival of new hippocampal neurons. The trillions of microorganisms resident to the gastrointestinal tract, collectively known as the gut microbiota, also demonstrate the ability to modulate adult hippocampal neurogenesis. In doing so, the microbiota-gut-brain axis can influence brain functions regulated by adult hippocampal neurogenesis. Unlike the hippocampus, the gut microbiota is highly accessible to direct interventions, such as prebiotics, probiotics, and antibiotics, and can be manipulated by lifestyle choices including diet. Therefore, understanding the pathways by which the gut microbiota shapes hippocampal neurogenesis may reveal novel targets for non-invasive therapeutics to treat disorders in which alterations in hippocampal neurogenesis have been implicated. This review first outlines the factors which influence both the gut microbiome and adult hippocampal neurogenesis, with cognizance that these effects might happen either independently or due to microbiota-driven mechanisms. We then highlight approaches for investigating the regulation of adult hippocampal neurogenesis by the microbiota-gut-brain axis. Finally, we summarize the current evidence demonstrating the gut microbiota's ability to influence adult hippocampal neurogenesis, including mechanisms driven through immune pathways, microbial metabolites, endocrine signalling, and the nervous system, and postulate implications for these effects in disease onset and treatment.
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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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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.