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Gut Microbiota and Pathophysiology of Depressive Disorder.
Kunugi, H
Annals of nutrition & metabolism. 2021;77 Suppl 2:11-20
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Bidirectional communication between the brain and gastrointestinal tract has been established and evidence suggests the microbiota-gut-brain axis may play a role in many psychiatric diseases, including major depression disorder (MDD). Although there is currently no established biochemical marker used in the clinical setting, recent findings have identified four potential mechanisms underlying MDD. The aim of this review is to outline these mechanisms and summarise the current evidence related to the pathophysiology of MDD. The literature suggests the gut microbiota impacts each of the potential mechanisms in the pathophysiology of MDD, and recent clinical trials on probiotics indicate beneficial effects on depression symptoms. Based on these results, the author concludes that practices leading to a healthier gut microbiota may aid in the reduction of depression symptoms. Future research on the microbiota-gut-brain axis in MDD is a promising avenue for better understanding the pathophysiology of disease and developing improved treatments for MDD.
Abstract
BACKGROUND Accumulating evidence has suggested that the bi-directional communication pathway, the microbiota-gut-brain axis, plays an important role in the pathophysiology of many neuropsychiatric diseases including major depressive disorder (MDD). This review outlines current evidence and promising findings related to the pathophysiology and treatment of MDD. SUMMARY There are at least 4 key biological molecules/systems underlying the pathophysiology of MDD: central dopamine, stress responses by the hypothalamic-pituitary-adrenal axis and autonomic nervous system, inflammation, and brain-derived neurotrophic factor. Animal experiments in several depression models have clearly indicated that gut microbiota is closely related to these molecules/systems and administration of probiotics and prebitotics may have beneficial effects on them. Although the results of microbiota profile of MDD patients varied from a study to another, multiple studies reported that bacteria which produce short-chain fatty acids such as butyrate and those protective against metabolic diseases (e.g., Bacteroidetes) were reduced. Clinical trials of probiotics have emerged, and the majority of the studies have reported beneficial effects on depression symptoms and related biological markers. Key Messages: The accumulating evidence suggests that research on the microbiota-gut-brain axis in major depressive disorder (MDD) is promising to elucidate the pathophysiology and to develop novel treatment of MDD, although there is still a long distance yet to reach the goals.
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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.
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Gut hormones in microbiota-gut-brain cross-talk.
Sun, LJ, Li, JN, Nie, YZ
Chinese medical journal. 2020;133(7):826-833
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The bidirectional communication between the gastrointestinal tract and the brain, termed the gut-brain axis (GBA), is evidenced to to play a role in physiological and psychological health. While precise communication pathways are not yet clear, it is hypothesised this pathway may be an important therapeutic target in complex psychiatric and gastrointestinal disorders. The aim of this review is to summarize the role of gut hormones in the GBA and focus on how the microbiota interact with these hormones in health and disease. The literature shows the gut microbiota can affect the metabolism of various gut hormones, and these hormones can influence the microbiota. Evidence suggests this cross-talk may be a key regulator in appetite, immune response, stress response, and metabolism. Based on this review, the authors conclude the gut microbiota-hormone homeostatic relationship provides insight on the complex communication between the gut and the brain. They suggest future research should target the microbiota-hormones-gut-brain axis to develop new therapeutic strategies to psychiatric disorders.
Abstract
The homeostasis of the gut-brain axis has been shown to exert several effects on physiological and psychological health. The gut hormones released by enteroendocrine cells scattered throughout the gastrointestinal tract are important signaling molecules within the gut-brain axis. The interaction between gut microbiota and gut hormones has been greatly appreciated in gut-brain cross-talk. The microbiota plays an essential role in modulating many gut-brain axis-related diseases, ranging from gastrointestinal disorders to psychiatric diseases. Similarly, gut hormones also play pleiotropic and important roles in maintaining health, and are key signals involved in gut-brain axis. More importantly, gut microbiota can affect the release and functions of gut hormones. This review highlights the role of gut microbiota in the gut-brain axis and focuses on how microbiota-related gut hormones modulate various physiological functions. Future studies could target the microbiota-hormones-gut brain axis to develop novel therapeutics for different psychiatric and gastrointestinal disorders, such as obesity, anxiety, and depression.
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Zinc, Magnesium, Selenium and Depression: A Review of the Evidence, Potential Mechanisms and Implications.
Wang, J, Um, P, Dickerman, BA, Liu, J
Nutrients. 2018;10(5)
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Adequate micronutrient consumption and mental health are of major public health importance. Recent findings suggest micronutrient deficiencies may play a role in the development and progression of depression, yet the findings remain unclear. The aim of this review is to present the recent evidence on the association between several micronutrients and depression and discuss the potential mechanisms and clinical implications. Based on the current literature, evidence shows an association between both zinc and magnesium deficiency and the risk of depression, with stronger evidence supporting zinc. Studies on selenium are limited or inconclusive. According to these findings, the authors support the importance of adequate micronutrient consumption for promoting mental health. They suggest future research should investigate the safety and efficacy of micronutrient supplementation as an adjunct treatment for depression to better inform current prevention and treatment strategies.
Abstract
Micronutrient deficiency and depression are major global health problems. Here, we first review recent empirical evidence of the association between several micronutrients—zinc, magnesium, selenium—and depression. We then present potential mechanisms of action and discuss the clinical implications for each micronutrient. Collectively, empirical evidence most strongly supports a positive association between zinc deficiency and the risk of depression and an inverse association between zinc supplementation and depressive symptoms. Less evidence is available regarding the relationship between magnesium and selenium deficiency and depression, and studies have been inconclusive. Potential mechanisms of action involve the HPA axis, glutamate homeostasis and inflammatory pathways. Findings support the importance of adequate consumption of micronutrients in the promotion of mental health, and the most common dietary sources for zinc and other micronutrients are provided. Future research is needed to prospectively investigate the association between micronutrient levels and depression as well as the safety and efficacy of micronutrient supplementation as an adjunct treatment for depression.
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Microbiome-Gut-Brain Axis and Toll-Like Receptors in Parkinson's Disease.
Caputi, V, Giron, MC
International journal of molecular sciences. 2018;19(6)
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Parkinson’s disease (PD) is a progressively debilitating neurodegenerative disease and recently the role of the microbiota-gut-brain axis has gained attention in patients with PD. Research shows that an altered gut microbiota can activate Toll-like receptors (TLRs), receptors involved in the innate immune response, causing an inflammatory cascade in the gut and brain. Based on this knowledge, gut microbiota and TLRs may be potential therapeutic targets for PD. This review sheds light on the current knowledge regarding the association between the microbiota-gut-brain axis and innate immunity via TLR signalling in PD. Increased understanding of this relationship should lead to insights on the pathophysiology of PD, as well as improved dietary and pharmaceutical therapeutic approaches in PD patients. Based on the existing evidence, the authors conclude that through modulating the gut, thus balancing the immune response in PD patients, it may be possible to influence early phases of the neurodegenerative cascade.
Abstract
Parkinson’s disease (PD) is a progressively debilitating neurodegenerative disease characterized by α-synucleinopathy, which involves all districts of the brain-gut axis, including the central, autonomic and enteric nervous systems. The highly bidirectional communication between the brain and the gut is markedly influenced by the microbiome through integrated immunological, neuroendocrine and neurological processes. The gut microbiota and its relevant metabolites interact with the host via a series of biochemical and functional inputs, thereby affecting host homeostasis and health. Indeed, a dysregulated microbiota-gut-brain axis in PD might lie at the basis of gastrointestinal dysfunctions which predominantly emerge many years prior to the diagnosis, corroborating the theory that the pathological process is spread from the gut to the brain. Toll-like receptors (TLRs) play a crucial role in innate immunity by recognizing conserved motifs primarily found in microorganisms and a dysregulation in their signaling may be implicated in α-synucleinopathy, such as PD. An overstimulation of the innate immune system due to gut dysbiosis and/or small intestinal bacterial overgrowth, together with higher intestinal barrier permeability, may provoke local and systemic inflammation as well as enteric neuroglial activation, ultimately triggering the development of alpha-synuclein pathology. In this review, we provide the current knowledge regarding the relationship between the microbiota-gut⁻brain axis and TLRs in PD. A better understanding of the dialogue sustained by the microbiota-gut-brain axis and innate immunity via TLR signaling should bring interesting insights in the pathophysiology of PD and provide novel dietary and/or therapeutic measures aimed at shaping the gut microbiota composition, improving the intestinal epithelial barrier function and balancing the innate immune response in PD patients, in order to influence the early phases of the following neurodegenerative cascade.
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Harnessing the Power of Microbiome Assessment Tools as Part of Neuroprotective Nutrition and Lifestyle Medicine Interventions.
Toribio-Mateas, M
Microorganisms. 2018;6(2)
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This is a practical review written by a clinician for other clinicians. It draws from an extensive body of evidence on the links between the gut microbes (bacteria amongst them), called the microbiota, both in health and in a variety of human diseases. The author, who is also a researcher in the communication between the gut and the brain (the gut-brain axis), focuses on the translation of science into simple clinical applications that result in measurable health outcomes, and in particular in neurodegenerative conditions such as Alzheimer's and Parkinson's, but also other less well studied such as Chronic Fatigue Syndrome (CFS). The paper also covers mental health / mood conditions such as anxiety, and depression. Practitioners who work in the area of gut health and use stool tests to assess various imbalances their patients may be experiencing will get the most out this paper. The author takes a look at the physiological processes that influence gastrointestinal as well as brain health and discusses how tools such as the characterisation or "mapping" of commensal bacteria (the bacteria that lives inside our guts normally), along with the identification of potential opportunistic and pathogenic bacteria and parasites, together with knowledge of molecules such as short chain fatty acids or zonulin can enable better clinical decision making by nutrition and lifestyle medicine practitioners. The paper also includes a valuable discussion on patient-reported outcome measures (PROMs), and particularly on the use of MYMOP by practitioners as a validated tool to collect insight from exposure to real world data in clinical practice.
Abstract
An extensive body of evidence documents the importance of the gut microbiome both in health and in a variety of human diseases. Cell and animal studies describing this relationship abound, whilst clinical studies exploring the associations between changes in gut microbiota and the corresponding metabolites with neurodegeneration in the human brain have only begun to emerge more recently. Further, the findings of such studies are often difficult to translate into simple clinical applications that result in measurable health outcomes. The purpose of this paper is to appraise the literature on a select set of faecal biomarkers from a clinician’s perspective. This practical review aims to examine key physiological processes that influence both gastrointestinal, as well as brain health, and to discuss how tools such as the characterisation of commensal bacteria, the identification of potential opportunistic, pathogenic and parasitic organisms and the quantification of gut microbiome biomarkers and metabolites can help inform clinical decisions of nutrition and lifestyle medicine practitioners.
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Intestinal microbiome-gut-brain axis and irritable bowel syndrome.
Moser, G, Fournier, C, Peter, J
Wiener medizinische Wochenschrift (1946). 2018;168(3-4):62-66
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The gut-brain-microbiota axis connects the nervous system with the metabolic, hormonal and immune functions of the intestines. Irritable bowel syndrome (IBS) is a functional gut disorder that commonly presents with psychological co-morbidities, and while animal studies show strong associations between stress and gut microbiota, studies in humans are rare. This review assesses the current literature on intestinal microbiome and its association with stress, anxiety and depression in patients with IBS. Based on existing studies, the authors found the gut microbiota forms a crucial link between the intestine and nervous system. Therapies targeted at both modulating the gut microbiome and psychological interventions are recommended. The authors conclude further randomised clinical trials are needed to better understand which therapies work best for patients with IBS.
Abstract
Psychological comorbidity is highly present in irritable bowel syndrome (IBS). Recent research points to a role of intestinal microbiota in visceral hypersensitivity, anxiety, and depression. Increased disease reactivity to psychological stress has been described too. A few clinical studies have attempted to identify features of dysbiosis in IBS. While animal studies revealed strong associations between stress and gut microbiota, studies in humans are rare. This review covers the most important studies on intestinal microbial correlates of psychological and clinical features in IBS, including stress, anxiety, and depression.