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Using psychoneuroimmunity against COVID-19.
Kim, SW, Su, KP
Brain, behavior, and immunity. 2020;87:4-5
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This viewpoint article raises awareness of the threat of COVID-19 poses to psychiatric patients who are in mental health hospitals. Those patients appear to have a much elevated mortality rate and are potentially more vulnerable to the effects of panic/anxiety due to the pandemic. Their lifestyle choices, influenced by fears about the virus, may also have a negative effect on their immunity. The article also raises the issue of the effects the pandemic and associated changes to day-to-day life can have on the mental and general health of the rest of the population, and in particular to mental health professionals, whose ability to care for their psychiatric patients may be impaired. The authors also briefly discuss the psychological and immunological mechanisms that connect our mental state to the ability of our immune system to fight infections, and the impact of our lifestyles and environments. To summarise they state that infected patients, uninfected quarantined individuals and medical professionals all require mental health supporting strategies, and that epidemiological studies of potential long-term psychiatric consequences are essential.
Abstract
The worldwide outbreak of coronavirus disease 2019 (COVID-19) raises concerns of widespread panic and anxiety in individuals subjected to the real or perceived threat of the virus. Compared to general populations, patients who are institutionalized in a closed unit are also very vulnerable to COVID-19 infection and complications. This crisis touched on difficult issues of not only psychiatric care and ethics, but also psychological impacts to psychiatric care givers. In this Viewpoint, we address both physical and biopsychosocial aspects of this infection, as well as the psychoneuroimmunity of preventive strategies of healthy lifestyle, regular exercise, balanced nutrition, quality sleep and a strong connection with people. Social distancing and wearing masks might help us from pathogen exposure, yet such these measures also prevent us from expressing compassion and friendliness. Therefore, all forms of psychological support should be routinely implemented not only to consider psychological resilience but also to enhance psychoneuroimmunity against COVID-19.
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Current Perspectives on Gut Microbiome Dysbiosis and Depression.
Capuco, A, Urits, I, Hasoon, J, Chun, R, Gerald, B, Wang, JK, Kassem, H, Ngo, AL, Abd-Elsayed, A, Simopoulos, T, et al
Advances in therapy. 2020;37(4):1328-1346
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The gut microbiome has been implicated in several neurological disorders; however exact mechanisms are still not fully understood. This review of recent studies, aimed to investigate the relationship between an imbalanced gut microbiome and depression. The authors first looked at the epidemiology of disease, concluding that significant burden needs to be assessed through improved preventative measures. This will depend upon the correct identification of risk factors, and the study focused on the role of the gut microbiome in this through animal and human studies. Imbalances in inflammation through altered gut microbiota, depleted biodiversity and stress induced microbiome changes were all implicated in the development of depression. It was concluded that studies on the role of microbiota in depression remain promising but are small and follow many different methodologies. This study could be used by healthcare professionals to better understand the role of gut microbiota in the development of depression and that ensuring a healthy gut may improve symptoms.
Abstract
The human gut microbiome partakes in a bidirectional communication pathway with the central nervous system (CNS), named the microbiota-gut-brain axis. The microbiota-gut-brain axis is believed to modulate various central processes through the vagus nerve as well as production of microbial metabolites and immune mediators which trigger changes in neurotransmission, neuroinflammation, and behavior. Little is understood about the utilization of microbiome manipulation to treat disease. Though studies exploring the role of the microbiome in various disease processes have shown promise, mechanisms remain unclear and evidence-based treatments for most illnesses have not yet been developed. The animal studies reviewed here offer an excellent array of basic science research that continues to clarify mechanisms by which the microbiome may affect mental health. More evidence is needed, particularly as it relates to translating this work to human subjects. The studies presented in this paper largely demonstrate encouraging results in the treatment of depression. Limitations include small sample sizes and heterogeneous methodology. The exact mechanism by which the gut microbiota causes or alters neuropsychiatric disease states is not fully understood. In this review, we focus on recent studies investigating the relationship between gut microbiome dysbiosis and the pathogenesis of depression. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.
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Mental Disorders Linked to Crosstalk between The Gut Microbiome and The Brain.
Choi, TY, Choi, YP, Koo, JW
Experimental neurobiology. 2020;29(6):403-416
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The gut microbiome may have a role in regular brain function and mental health and this review paper aimed to determine the mechanisms through which this may be possible. There are several mental health disorders that may be affected by the gut microbiome, major depressive disorder (MDD), anxiety disorder, autism spectrum disorder (ASD), Alzheimer’s disease (AD), and addiction. It appears that there is a correlation between a disordered gut microbiome (known as dysbiosis) and MDD, ASD and addiction. Anxiety symptoms in healthy individuals and cognitive deficits in individuals with AD have reportedly been improved with probiotics. How the gut microbiome communicates with the brain was also discussed with the enteric nervous system, vagus nerve, spinal chord, immune system and brain signalling molecules all being implicated as possible routes. Finally, the paper discussed the use of probiotics for the prevention or treatment of mental disorders, with Bifidobacteria, Lactobacillus and specifically L. reuteri, L. plantarum and L. helveticus all shown in animal models to improve aspects associated with mental disorders. Amongst the human research B. longum has been shown to relieve stress and increase cognitive function in healthy individuals. It was concluded that studies have elucidated a relationship between the gut microbiome and mental health through various routes of communication. Research should focus on how gut microbiome changes are involved in mental illness. This study could be used by healthcare professionals to further knowledge on the potential relationship between the gut microbiome and mental health.
Abstract
Often called the second brain, the gut communicates extensively with the brain and vice versa. The conversation between these two organs affects a variety of physiological mechanisms that are associated with our mental health. Over the past decade, a growing body of evidence has suggested that the gut microbiome builds a unique ecosystem inside the gastrointestinal tract to maintain the homeostasis and that compositional changes in the gut microbiome are highly correlated with several mental disorders. There are ongoing efforts to treat or prevent mental disorders by regulating the gut microbiome using probiotics. These attempts are based on the seminal findings that probiotics can control the gut microbiome and affect mental conditions. However, some issues have yet to be conclusively addressed, especially the causality between the gut microbiome and mental disorders. In this review, we focus on the mechanisms by which the gut microbiome affects mental health and diseases. Furthermore, we discuss the potential use of probiotics as therapeutic agents for psychiatric disorders.
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Bacterial Metabolites of Human Gut Microbiota Correlating with Depression.
Averina, OV, Zorkina, YA, Yunes, RA, Kovtun, AS, Ushakova, VM, Morozova, AY, Kostyuk, GP, Danilenko, VN, Chekhonin, VP
International journal of molecular sciences. 2020;21(23)
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Depression is multifactorial disease and it is the most common type of psychiatric disorder. Literature indicates that there are significant differences between the gut microbiota (GM) of patients with depression and healthy controls. The aim of this review was to examine (a) various low-molecular compounds as potential biomarkers of depression in correlation with the metabolism of the GM, and (b) ways to correct the microbiota imbalance. Results show that: - the use of the GM biomarkers, reflecting the neuromodulatory [the process by which nervous activity is regulated through classes of neurotransmitters], immunomodulatory [the process by which the body’s immune system is altered] and antioxidant statuses of the host organism, in the analysis of metagenomic [the study of a collection of genetic material (genomes) from a mixed community of organisms] data from patients with neuropsychiatric diseases, is gaining currency. - diet remains one of the most effective measures that can be taken to restore the microbial balance in the gut and alleviate the symptoms of depression. - a healthy diet during the depression therapy, along with the application of probiotics and psychobiotics, may potentially improve the course of the disease and contribute to the progress of treatment. Authors conclude that further progress in the practical understanding of the role of the GM in depression will greatly depend on correct planning of future metagenomic studies.
Abstract
Depression is a global threat to mental health that affects around 264 million people worldwide. Despite the considerable evolution in our understanding of the pathophysiology of depression, no reliable biomarkers that have contributed to objective diagnoses and clinical therapy currently exist. The discovery of the microbiota-gut-brain axis induced scientists to study the role of gut microbiota (GM) in the pathogenesis of depression. Over the last decade, many of studies were conducted in this field. The productions of metabolites and compounds with neuroactive and immunomodulatory properties among mechanisms such as the mediating effects of the GM on the brain, have been identified. This comprehensive review was focused on low molecular weight compounds implicated in depression as potential products of the GM. The other possible mechanisms of GM involvement in depression were presented, as well as changes in the composition of the microbiota of patients with depression. In conclusion, the therapeutic potential of functional foods and psychobiotics in relieving depression were considered. The described biomarkers associated with GM could potentially enhance the diagnostic criteria for depressive disorders in clinical practice and represent a potential future diagnostic tool based on metagenomic technologies for assessing the development of depressive disorders.
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The Role of Bacteria and Its Derived Metabolites in Chronic Pain and Depression: Recent Findings and Research Progress.
Li, S, Hua, D, Wang, Q, Yang, L, Wang, X, Luo, A, Yang, C
The international journal of neuropsychopharmacology. 2020;23(1):26-41
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Depression is closely associated with chronic pain yet the connection between these comorbidities is ambiguous. Recent studies have shown alterations in the gut microbiome may contribute to cognitive dysfunction via the microbiota-gut-brain axis. The aim of this systematic review is to summarize the existing evidence of the role of the gut microbiome in chronic pain and depression and explore potential mechanisms of gut dysbiosis in the development of these conditions. This review found metabolic products from the gut microbiota can mediate neuro-inflammation and neuro-immunity pathways in pain and depression, and that dysbiosis in the gut may contribute to the cause of chronic pain and depression. The authors conclude the metabolic products from the gut bacteria offer new insights to the connection between the gut microbiota and mechanisms of pain and depression, while showing potential as a therapeutic target.
Abstract
BACKGROUND Chronic pain is frequently comorbid with depression in clinical practice. Recently, alterations in gut microbiota and metabolites derived therefrom have been found to potentially contribute to abnormal behaviors and cognitive dysfunction via the "microbiota-gut-brain" axis. METHODS PubMed was searched and we selected relevant studies before October 1, 2019. The search keyword string included "pain OR chronic pain" AND "gut microbiota OR metabolites"; "depression OR depressive disorder" AND "gut microbiota OR metabolites". We also searched the reference lists of key articles manually. RESULTS This review systematically summarized the recent evidence of gut microbiota and metabolites in chronic pain and depression in animal and human studies. The results showed the pathogenesis and therapeutics of chronic pain and depression might be partially due to gut microbiota dysbiosis. Importantly, bacteria-derived metabolites, including short-chain fatty acids, tryptophan-derived metabolites, and secondary bile acids, offer new insights into the potential linkage between key triggers in gut microbiota and potential mechanisms of depression. CONCLUSION Studying gut microbiota and its metabolites has contributed to the understanding of comorbidity of chronic pain and depression. Consequently, modulating dietary structures or supplementation of specific bacteria may be an available strategy for treating chronic pain and depression.
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Pilot trial of a group cognitive behavioural therapy program for comorbid depression and obesity.
Lores, T, Musker, M, Collins, K, Burke, A, Perry, SW, Wong, ML, Licinio, J
BMC psychology. 2020;8(1):34
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Depression and obesity are significant global health concerns. Depression can significantly impact physical health and reduced immune function. The aim of this study was to examine the potential benefits of a novel group psychological intervention program. The study is a preliminary quasi-experimental (single-arm) before-after pilot trial of a newly developed group-based psychological intervention program for people with depression and comorbid obesity. The program consisted of 10 two-hour group sessions held weekly. A total of 24 participants were recruited to the program across two pilot groups. Results indicate that there was a significant reduction in participants’ depression and anxiety scores by program-end. Some evidence also shows improvements in weight-related negative cognitions. Authors conclude that the group therapy program therefore has considerable potential to be effective in helping people enjoy better mental health and improve health outcomes.
Abstract
BACKGROUND Depression and obesity are significant global health concerns that commonly occur together. An integrated group cognitive behavioural therapy program was therefore developed to simultaneously address comorbid depression and obesity. METHODS Twenty-four participants (63% women, mean age 46 years) who screened positively for depression with a body mass index ≥25 were recruited from a self-referred general population sample. The group therapy program (10 two-hour weekly sessions) was examined in a single-arm, before-after pilot trial, conducted in a behavioural health clinic in Adelaide, Australia. Primary outcomes included survey and assessment-based analyses of depression, anxiety, body image, self-esteem, and weight (kg), assessed at four time-points: baseline, post-intervention, three-months and 12-months post program. Eighteen participants (75%) completed the program and all assessments. RESULTS Significant improvements in depression, anxiety, self-esteem and body shape concern scores, several quality of life domains, eating behaviours and total physical activity (among others) - but not weight - were observed over the course of the trial. CONCLUSIONS Results from this pilot trial suggest that combining interventions for depression and obesity may be useful. Further development of the program, particularly regarding the potential for physical health benefits, and a randomised controlled trial, are warranted. TRIAL REGISTRATION Trial registration: ANZCTR, ACTRN12617001079336, 13 July 2017. Retrospectively registered after date of the first consent (6 July 2017), but before the date of the first intervention session (20 July 2017).
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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.
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Recognizing Depression from the Microbiota⁻Gut⁻Brain Axis.
Liang, S, Wu, X, Hu, X, Wang, T, Jin, F
International journal of molecular sciences. 2018;19(6)
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Emerging research indicates that major depression is not just a mental disorder but also a systemic disease. In depression, the brain-gut axis, the bidirectional pathway that connects the brain and gut, is thought to be disturbed. This disruption is hypothesised to be a major pathological basis of depression. The aim of this paper is to explore this hypothesis by reviewing the current literature. According to the current literature, the authors found research stating the gut microbiota of depressed patients is significantly different from that of healthy controls. Additionally, disturbances or abnormalities in the gut can influence the susceptibility of onset of depression, while restoration of the gut will alleviate depression. Based on these findings, the authors conclude depression is closely related with the condition of the brain-gut axis, and that restoring the normal condition of gut microbiota may aid in the therapy of depression. The authors expect therapies that target gut microbiota will play an important role in the treatment and prevention of depression in the future.
Abstract
Major depression is one of the leading causes of disability, morbidity, and mortality worldwide. The brain⁻gut axis functions are disturbed, revealed by a dysfunction of the brain, immune system, endocrine system, and gut. Traditional depression treatments all target the brain, with different drugs and/or psychotherapy. Unfortunately, most of the patients have never received any treatment. Studies indicate that gut microbiota could be a direct cause for the disorder. Abnormal microbiota and the microbiota⁻gut⁻brain dysfunction may cause mental disorders, while correcting these disturbance could alleviate depression. Nowadays, the gut microbiota modulation has become a hot topic in treatment research of mental disorders. Depression is closely related with the health condition of the brain⁻gut axis, and maintaining/restoring the normal condition of gut microbiota helps in the prevention/therapy of mental disorders.
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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.