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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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The Gut Microbiome and Mental Health: What Should We Tell Our Patients?: Le microbiote Intestinal et la Santé Mentale : que Devrions-Nous dire à nos Patients?
Butler, MI, Mörkl, S, Sandhu, KV, Cryan, JF, Dinan, TG
Canadian journal of psychiatry. Revue canadienne de psychiatrie. 2019;64(11):747-760
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The gut-brain axis is the bi-directional communication pathway and increasing evidence indicates its impact in neural health and disease. With the field of nutritional psychiatry actively developing, psychiatric patients have become increasingly aware of the therapeutic use of probiotics and mental health. This review aims to inform psychiatrists about the communication between the microbiome and brain and discuss its relevance to the management and treatment of psychiatric illness. In reviewing the common psychiatric illnesses, the current literature shows inconsistent results on specific microbiome compositions related to specific illnesses, yet shows promising effects for probiotic use in many disorders. These findings offer a novel paradigm for approaching mental illness through the lens of nutritional psychiatry. Authors conclude there is much work to be done translating laboratory findings into clinical practice, and highlight the necessity for clinicians to stay informed of the literature and make accurate recommendations to patients.
Abstract
The gut microbiome as a potential therapeutic target for mental illness is a hot topic in psychiatry. Trillions of bacteria reside in the human gut and have been shown to play a crucial role in gut-brain communication through an influence on neural, immune, and endocrine pathways. Patients with various psychiatric disorders including depression, bipolar disorder, schizophrenia, and autism spectrum disorder have been shown to have significant differences in the composition of their gut microbiome. Enhancing beneficial bacteria in the gut, for example, through the use of probiotics, prebiotics, or dietary change, has the potential to improve mood and reduce anxiety in both healthy people and patient groups. Much attention is being given to this subject in the general media, and patients are becoming increasingly interested in the potential to treat mental illness with microbiome-based therapies. It is imperative that those working with people with mental illness are aware of the rationale and current evidence base for such treatment strategies. In this review, we provide an overview of the gut microbiome, what it is, and what it does in relation to gut-brain communication and psychological function. We describe the fundamental principles and basic techniques used in microbiome-gut-brain axis research in an accessible way for a clinician audience. We summarize the current evidence in relation to microbiome-based strategies for various psychiatric disorders and provide some practical advice that can be given to patients seeking to try a probiotic for mental health benefit.
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Anxiety, Depression, and the Microbiome: A Role for Gut Peptides.
Lach, G, Schellekens, H, Dinan, TG, Cryan, JF
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. 2018;15(1):36-59
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Hormones released in the gut can have an impact in the brain through a bidirectional relationship, known as the gut-brain axis. The release of these hormones may be controlled by the gut microbiota, however exact mechanisms are not fully understood. Most hormones originating in the gut may have a role in obesity development, which is often associated with psychiatric disorders. Understanding the relationship between gut microbiota and depression through gut derived signalling molecules may be of benefit and was the focus of this review. Diversity and stability of the gut microbiota is important for health, which is disrupted during depression and anxiety. The gut microbiota serves to produce brain, hormone and immune signals that can travel to the brain, and can be affected by poor gut health. For those with depression, side effects of anti-depressants can be a disruption of the gut microbiota, however how this impacts symptoms is not fully understood. It was concluded that although there is strong research on the gut microbiota and depression it is still in its infancy. The role of gut microbiota on signalling with the brain and the rest of the body seems to be important for depression and anxiety. This study could be used by healthcare professionals to understand how the gut microbiota can play a role in depression.
Abstract
The complex bidirectional communication between the gut and the brain is finely orchestrated by different systems, including the endocrine, immune, autonomic, and enteric nervous systems. Moreover, increasing evidence supports the role of the microbiome and microbiota-derived molecules in regulating such interactions; however, the mechanisms underpinning such effects are only beginning to be resolved. Microbiota-gut peptide interactions are poised to be of great significance in the regulation of gut-brain signaling. Given the emerging role of the gut-brain axis in a variety of brain disorders, such as anxiety and depression, it is important to understand the contribution of bidirectional interactions between peptide hormones released from the gut and intestinal bacteria in the context of this axis. Indeed, the gastrointestinal tract is the largest endocrine organ in mammals, secreting dozens of different signaling molecules, including peptides. Gut peptides in the systemic circulation can bind cognate receptors on immune cells and vagus nerve terminals thereby enabling indirect gut-brain communication. Gut peptide concentrations are not only modulated by enteric microbiota signals, but also vary according to the composition of the intestinal microbiota. In this review, we will discuss the gut microbiota as a regulator of anxiety and depression, and explore the role of gut-derived peptides as signaling molecules in microbiome-gut-brain communication. Here, we summarize the potential interactions of the microbiota with gut hormones and endocrine peptides, including neuropeptide Y, peptide YY, pancreatic polypeptide, cholecystokinin, glucagon-like peptide, corticotropin-releasing factor, oxytocin, and ghrelin in microbiome-to-brain signaling. Together, gut peptides are important regulators of microbiota-gut-brain signaling in health and stress-related psychiatric illnesses.