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Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders.
Chen, Y, Xu, J, Chen, Y
Nutrients. 2021;13(6)
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Imbalances in the gut microbiota occur in various neurological disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), autism spectrum disorder and depression. Imbalances in key neurotransmitters are associated with the same disorders. This review focuses on the regulatory mechanisms of the intestinal microbiome and its metabolites on cognitive functions and the pathogeneses of these neurodegenerative diseases. The gut microbiota produce neurotransmitters such as glutamate, GABA, serotonin and dopamine or their precursors. These neurotransmitters are not able to cross the blood brain barrier but the precursors are, therefore the gut microbiota is indirectly involved in the regulation of the production of these key neurotransmitters and therefore neuronal activity and cognitive functions of the brain. The findings demonstrate an association between a healthy gut microbiome structure and balanced neurotransmitter levels in the host. Microbial therapy holds huge promise for the treatment of brain disorders. The development of drugs for neurological disorders must also consider effects on the physiology of the gut microbiome.
Abstract
Emerging evidence indicates that gut microbiota is important in the regulation of brain activity and cognitive functions. Microbes mediate communication among the metabolic, peripheral immune, and central nervous systems via the microbiota-gut-brain axis. However, it is not well understood how the gut microbiome and neurons in the brain mutually interact or how these interactions affect normal brain functioning and cognition. We summarize the mechanisms whereby the gut microbiota regulate the production, transportation, and functioning of neurotransmitters. We also discuss how microbiome dysbiosis affects cognitive function, especially in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.
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Towards Tailored Gut Microbiome-Based and Dietary Interventions for Promoting the Development and Maintenance of a Healthy Brain.
Larroya, A, Pantoja, J, Codoñer-Franch, P, Cenit, MC
Frontiers in pediatrics. 2021;9:705859
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The cause of neurodevelopmental disorders (NDDs) is complex and multifactorial. Recent studies have indicated that early life disturbances of the gut microbiome can impact neurodevelopment, suggesting this critical window may play a key role in the prevention or progression of neurological disease. The growing field of personalized nutrition works on the basis of tailored dietary intervention strategies that consider individual variability based on genetics, diet, and the environment. The aim of this paper is to review the current evidence on the neurodevelopmental interaction between the gut microbiota, environment and host, and assess the efficacy of tailored, personalized nutrition interventions aimed at preventing or treating NDDs. The literature provides evidence that the gut microbiota is susceptible to influence by various factors early in life, and the health of the microbiome may modulate mental health consequences later in life. Additionally, key nutritional deficiencies and microbiome alterations have been linked to NDDs, suggesting potential markers that may lead to improved prevention and treatment. Based on the current literature, the authors emphasize the need for further research during the critical window of microbiome development in order to target the cause of neurodevelopmental impairments. They suggest these findings could help progress the field of Nutritional Psychiatry towards effective tailored nutrition and personalized medicine.
Abstract
Mental health is determined by a complex interplay between the Neurological Exposome and the Human Genome. Multiple genetic and non-genetic (exposome) factors interact early in life, modulating the risk of developing the most common complex neurodevelopmental disorders (NDDs), with potential long-term consequences on health. To date, the understating of the precise etiology underpinning these neurological alterations, and their clinical management pose a challenge. The crucial role played by diet and gut microbiota in brain development and functioning would indicate that modulating the gut-brain axis may help protect against the onset and progression of mental-health disorders. Some nutritional deficiencies and gut microbiota alterations have been linked to NDDs, suggesting their potential pathogenic implications. In addition, certain dietary interventions have emerged as promising alternatives or adjuvant strategies for improving the management of particular NDDs, at least in particular subsets of subjects. The gut microbiota can be a key to mediating the effects of other exposome factors such as diet on mental health, and ongoing research in Psychiatry and Neuropediatrics is developing Precision Nutrition Models to classify subjects according to a diet response prediction based on specific individual features, including microbiome signatures. Here, we review current scientific evidence for the impact of early life environmental factors, including diet, on gut microbiota and neuro-development, emphasizing the potential long-term consequences on health; and also summarize the state of the art regarding the mechanisms underlying diet and gut microbiota influence on the brain-gut axis. Furthermore, we describe the evidence supporting the key role played by gut microbiota, diet and nutrition in neurodevelopment, as well as the effectiveness of certain dietary and microbiome-based interventions aimed at preventing or treating NDDs. Finally, we emphasize the need for further research to gain greater insight into the complex interplay between diet, gut microbiome and brain development. Such knowledge would help towards achieving tailored integrative treatments, including personalized nutrition.
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The role of the microbiota-gut-brain axis in neuropsychiatric disorders.
Generoso, JS, Giridharan, VV, Lee, J, Macedo, D, Barichello, T
Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999). 2021;43(3):293-305
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Metabolites produced by the gut microbiota have been shown to influence mood and behaviour via the microbiota-gut-brain axis, and there is increased interest in better understanding this interaction in the context of mental health. This review summarises the evidence around the influence of gut microbiota in various neuropsychiatric disorders, primarily focusing on the metabolic pathways that originate in the gut microbiota. Current research highlights an association between gut microbiota metabolites with neuropsychiatric disorders and that probiotics demonstrate a significant therapeutic role in many of these disorders. Based on the current literature, the authors conclude it is crucial to better understand the complex microbiota-host interaction in health and disease, leading to more targeted and improved therapeutic interventions.
Abstract
The microbiota-gut-brain axis is a bidirectional signaling mechanism between the gastrointestinal tract and the central nervous system. The complexity of the intestinal ecosystem is extraordinary; it comprises more than 100 trillion microbial cells that inhabit the small and large intestine, and this interaction between microbiota and intestinal epithelium can cause physiological changes in the brain and influence mood and behavior. Currently, there has been an emphasis on how such interactions affect mental health. Evidence indicates that intestinal microbiota are involved in neurological and psychiatric disorders. This review covers evidence for the influence of gut microbiota on the brain and behavior in Alzheimer disease, dementia, anxiety, autism spectrum disorder, bipolar disorder, major depressive disorder, Parkinson's disease, and schizophrenia. The primary focus is on the pathways involved in intestinal metabolites of microbial origin, including short-chain fatty acids, tryptophan metabolites, and bacterial components that can activate the host's immune system. We also list clinical evidence regarding prebiotics, probiotics, and fecal microbiota transplantation as adjuvant therapies for neuropsychiatric disorders.
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Mining microbes for mental health: Determining the role of microbial metabolic pathways in human brain health and disease.
Spichak, S, Bastiaanssen, TFS, Berding, K, Vlckova, K, Clarke, G, Dinan, TG, Cryan, JF
Neuroscience and biobehavioral reviews. 2021;125:698-761
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The microbiota-gut-brain axis is an emerging area of focus for mental health and disease. Metabolic products from gut microbiota exert direct and indirect effects on the brain through various body systems. The aim of this study was to review the evidence on these metabolic pathways and utilise new predictive tools to assess metabolic signatures of various disease states. This review included 278 studies and, despite the weak evidence, identified new links between gut microbial metabolic pathways in schizophrenia, Alzheimer’s disease, and anxiety and depression. The authors conclude this review provides a novel approach for understanding the mechanisms behind the bidirectional communication between the gut and brain. They also suggest guidelines for analysing and interpreting metadata of human-microbiome-brain studies and provide a framework for better understanding these metabolic pathways in relation to the brain.
Abstract
There is increasing knowledge regarding the role of the microbiome in modulating the brain and behaviour. Indeed, the actions of microbial metabolites are key for appropriate gut-brain communication in humans. Among these metabolites, short-chain fatty acids, tryptophan, and bile acid metabolites/pathways show strong preclinical evidence for involvement in various aspects of brain function and behaviour. With the identification of neuroactive gut-brain modules, new predictive tools can be applied to existing datasets. We identified 278 studies relating to the human microbiota-gut-brain axis which included sequencing data. This spanned across psychiatric and neurological disorders with a small number also focused on normal behavioural development. With a consistent bioinformatics pipeline, thirty-five of these datasets were reanalysed from publicly available raw sequencing files and the remainder summarised and collated. Among the reanalysed studies, we uncovered evidence of disease-related alterations in microbial metabolic pathways in Alzheimer's Disease, schizophrenia, anxiety and depression. Amongst studies that could not be reanalysed, many sequencing and technical limitations hindered the discovery of specific biomarkers of microbes or metabolites conserved across studies. Future studies are warranted to confirm our findings. We also propose guidelines for future human microbiome analysis to increase reproducibility and consistency within the field.
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Molecular Mechanisms Underlying the Beneficial Effects of Exercise on Brain Function and Neurological Disorders.
Nay, K, Smiles, WJ, Kaiser, J, McAloon, LM, Loh, K, Galic, S, Oakhill, JS, Gundlach, AL, Scott, JW
International journal of molecular sciences. 2021;22(8)
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Exercise as therapy for mental health disorders has become common due to its reported benefits and low cost. There are many biological ways in which exercise may help mood disorders and diseases associated with brain degeneration and this review article aimed to highlight these. The authors first highlighted the research indicating that exercise may be protective in mood disorders with studies showing reduction of symptoms of depression, anxiety, schizophrenia, autism, and bipolar disorder. Exercise may also be of benefit in several brain degenerative disorders with studies indicating a positive impact in individuals with Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and Multiple Sclerosis. Studies have also indicated that individuals with brain injuries, such as stroke may also benefit. Several reasons for this were highlighted. When muscle is stimulated during exercise a key brain signalling molecule may be produced, known as brain-derived neurotrophic factor (BDNF). BDNF may have the effect of preventing brain degeneration and promoting regeneration. Exercise may also increase gut microbial diversity and increase beneficial bacteria which may benefit the brain in several ways. It was concluded that exercise may have beneficial effects for individuals with brain disorders. This study could be used by healthcare professionals to understand how exercise may be of benefit to individuals with mood disorders, brain degenerative diseases and brain injuries as part of a holistic treatment plan.
Abstract
As life expectancy has increased, particularly in developed countries, due to medical advances and increased prosperity, age-related neurological diseases and mental health disorders have become more prevalent health issues, reducing the well-being and quality of life of sufferers and their families. In recent decades, due to reduced work-related levels of physical activity, and key research insights, prescribing adequate exercise has become an innovative strategy to prevent or delay the onset of these pathologies and has been demonstrated to have therapeutic benefits when used as a sole or combination treatment. Recent evidence suggests that the beneficial effects of exercise on the brain are related to several underlying mechanisms related to muscle-brain, liver-brain and gut-brain crosstalk. Therefore, this review aims to summarize the most relevant current knowledge of the impact of exercise on mood disorders and neurodegenerative diseases, and to highlight the established and potential underlying mechanisms involved in exercise-brain communication and their benefits for physiology and brain function.
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Gut microbes in neurocognitive and mental health disorders.
Halverson, T, Alagiakrishnan, K
Annals of medicine. 2020;52(8):423-443
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Adequately and effectively treating and managing neurocognitive disorders remains a challenge. Increasing evidence suggests gut microbes may contribute to common mental health disorders through the microbiota-gut-brain axis, and better understanding this interaction could lead to improved clinical outcomes. The aim of this review is to discuss the impact of the gut microbiome on neurocognitive and mental health disorders and the mechanisms by which they act. This review reveals that the gut microbiome can influence brain and intestinal cells and that there is an association between gut dysbiosis with different mental health and neurocognitive disorders. Additionally, evidence shows the antimicrobial effect of current pharmaceutical treatments used in mental disorders may adversely affect the gut microbiome. Based on these findings, the authors conclude the gut microbiome is likely involved in the pathophysiology of neurocognitive and mental health conditions. Treatment strategies focusing on the gut microbiome may have a role in the treatment and management of mental health disorders, however further evidence is needed before applying these strategies in clinical practice.
Abstract
INTRODUCTION As individuals age, the prevalence of neurocognitive and mental health disorders increases. Current biomedical treatments do not completely address the management of these conditions. Despite new pharmacological therapy the challenges of managing these diseases remain.There is increasing evidence that the Gut Microbiome (GM) and microbial dysbiosis contribute to some of the more prevalent mental health and neurocognitive disorders, such as depression, anxiety, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), schizophrenia, bipolar disorder (BP), and dementia as well as the behavioural and psychological symptoms of dementia (BPSD) through the microbiota-gut-brain axis. Methodology: Scoping review about the effect of gut microbiota on neurocognitive and mental health disorders. RESULTS This scoping review found there is an evolving evidence of the involvement of the gut microbiota in the pathophysiology of neurocognitive and mental health disorders. This manuscript also discusses how the psychotropics used to treat these conditions may have an antimicrobial effect on GM, and the potential for new strategies of management with probiotics and faecal transplantation. CONCLUSIONS This understanding can open up the need for a gut related approach in these disorders as well as unlock the door for the role of gut related microbiota management. KEY MESSAGES Challenges of managing mental health conditions remain in spite of new pharmacological therapy. Gut dysbiosis is seen in various mental health conditions. Various psychotropic medications can have an influence on the gut microbiota by their antimicrobial effect.