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A randomized trial of probiotic supplementation in nurses to reduce stress and viral illness.
Slykerman, RF, Li, E
Scientific reports. 2022;12(1):14742
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Dynamic communication occurs between the gut microbiota and the central nervous system along multiple physiological pathways. Stress increases glucocorticoid production and activation of the hypothalamic–pituitary–adrenal axis, affecting immunological function and neuronal changes. The aim of this study was to investigate whether supplementation with the probiotic Lactobacillus rhamnosus HN001 could reduce symptoms of stress and anxiety and improve psychological wellbeing in nurses working during the COVID19 pandemic. This study was a large double-blind, placebo-controlled randomised trial of probiotic supplementation with two parallel arms and a ratio of allocation to probiotic or placebo of 1:1. Results showed that following the intervention, stress, anxiety, and psychological wellbeing were not significantly different between nurses supplemented with the probiotic and those who received the placebo. Furthermore, the average number of days per week that nurses reported symptoms of cold or flu-like illness did not significantly differ between the probiotic and placebo supplemented groups. Authors conclude that there weren’t significant differences in outcomes between the probiotic and placebo groups.
Abstract
Animal studies demonstrate how the gut microbiota influence psychological health and immunity to viral infections through their actions along multiple dynamic pathways in the body. Considerable interest exists in probiotics to reduce stress and illness symptoms through beneficial effects in the gut, but translating pre-clinical evidence from animal models into humans remains challenging. We conducted a large trial in nurses working during the 2020 COVID19 pandemic year to establish whether daily ingestion of the probiotic Lactobacillus rhamnosus HN001 reduced perceived stress and the number of days participants reported symptoms of a viral illness. Our results showed no significant difference in perceived stress or the average number of illness days between probiotic supplemented nurses and the placebo group. Stress and viral illness symptoms reduced during the study for all participants, a trajectory likely influenced by societal-level factors. The powerful effect of a well-managed public health response to the COVID19 pandemic and the elimination of COVID19 from the community in 2020 may have altered the trajectory of stress levels and reduced circulating viral infections making it difficult to detect any effect of probiotic supplementation. Our study highlights the challenge in controlling environmental factors in human trials.
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'Long COVID': persistent COVID-19 symptoms in survivors managed in Lagos State, Nigeria.
Osikomaiya, B, Erinoso, O, Wright, KO, Odusola, AO, Thomas, B, Adeyemi, O, Bowale, A, Adejumo, O, Falana, A, Abdus-Salam, I, et al
BMC infectious diseases. 2021;21(1):304
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The spectrum of clinical presentation of COVID-19 ranges from the asymptomatic, to symptomatic with varying levels of severity depending on age, comorbid conditions, and basal metabolic index. The aim of this study was to highlight associations between socio-demographic characteristics and comorbidities with persistent symptoms in COVID-19 survivors. This study is a retrospective study using de-identified data of 274 COVID-19 survivors. A thorough clinical history and physical assessment was conducted for all patients. Results indicate that: - the most common symptom manifested by survivors was easy fatigability. - neurologic symptoms were found in 39.1% of the COVID-19 survivors. Symptoms included headaches, insomnia, and attention deficits. - there was no significant association between demographic factors and comorbidities such as hypertension or diabetes and the presence of persistent symptoms in COVID-19 survivors. Authors conclude these findings, together with evidence from other studies, can guide policies and interventions aimed at improving the quality of life of survivors and return to usual health.
Abstract
BACKGROUND Coronavirus disease once thought to be a respiratory infection is now recognised as a multi-system disease affecting the respiratory, cardiovascular, gastrointestinal, neurological, immune, and hematopoietic systems. An emerging body of evidence suggests the persistence of COVID-19 symptoms of varying patterns among some survivors. This study aimed to describe persistent symptoms in COVID-19 survivors and investigate possible risk factors for these persistent symptoms. METHODS The study used a retrospective study design. The study population comprised of discharged COVID-19 patients. Demographic information, days since discharge, comorbidities, and persistent COVID-19 like symptoms were assessed in patients attending the COVID-19 outpatient clinic in Lagos State. Statistical analysis was done using STATA 15.0 software (StataCorp Texas) with significance placed at p-value < 0.05. RESULTS A total of 274 patients were enrolled in the study. A majority were within the age group > 35 to ≤49 years (38.3%), and male (66.1%). More than one-third (40.9%) had persistent COVID-19 symptoms after discharge, and 19.7% had more than three persistent COVID-like symptoms. The most persistent COVID-like symptoms experienced were easy fatigability (12.8%), headaches (12.8%), and chest pain (9.8%). Symptomatic COVID-19 disease with moderate severity compared to mild severity was a predictor of persistent COVID-like symptoms after discharge (p < 0.05). CONCLUSION Findings from this study suggests that patients who recovered from COVID-19 disease may still experience COVID-19 like symptoms, particularly fatigue and headaches. Therefore, careful monitoring should be in place after discharge to help mitigate the effects of these symptoms and improve the quality of life of COVID-19 survivors.
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Evaluation of COVID-19 Disease Awareness and Its Relation to Mental Health, Dietary Habits, and Physical Activity: A Cross-Sectional Study from Pakistan.
Ali, A, Sohaib, M, Iqbal, S, Hayat, K, Khan, AU, Rasool, MF
The American journal of tropical medicine and hygiene. 2021;104(5):1687-1693
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Dietary factors and healthy eating habits play a crucial role in human health management. The global pandemic of COVID-19 has significantly changed the dietary patterns and eating habits of the people worldwide, particularly in the area affected by this pandemic. The aim of this study was to assess the knowledge of COVID-19 disease and its association with anxiety, depression, dietary habits, and physical activity during the COVID-19 lockdown. This study was a descriptive cross-sectional survey conducted in the Punjab Province of Pakistan. A total of 1956 participants took part in the study. Results indicate that: - only 7.4% of participants had good knowledge about COVID-19. - the physical activity of the participants was affected as 66.9% of the participants had a decrease in physical activity and around 40% of the participants also gained weight. - around 70% of the participants were suffering from anxiety, and 52% were depressed. Authors conclude that their findings can help formulate concrete policy-making for the Pakistani population in terms of public health prospects. Furthermore, mass-level educational programmes should be launched via print and electronic media to enhance public awareness about COVID-19 and to improve dietary behaviour of people.
Abstract
Coronavirus infection (COVID-19) has significantly increased the mortality and morbidity rates worldwide. The present study was conducted to assess the general public's awareness of COVID-19 and its association with mental health, dietary habits, and physical activity. A web-based survey was conducted to gather information about demographics, knowledge about COVID-19, dietary habits, mental health, and anthropometry among the general public of Pakistan. Descriptive statistics, chi-square test, and multiple logistic regression were used for data analysis. The majority of the participants were suffering from anxiety (71.0%) and depression (52.0%) during the COVID-19 pandemic; 32.4% of participants had poor COVID-19-related knowledge. COVID-19 lockdown reduced the physical activity of 66.9% of participants and increased weight of 38.8% of the survey participants. Demographic variables, including age, gender, ethnicity, education, employment, family type, and geographical location, were significantly associated with knowledge about COVID-19 (P < 0.05). Depression was inversely associated with COVID-19 knowledge (P < 0.05). Healthy changes in dietary habits including decreased consumption of fast foods, soft and cola drinks, fruit drinks, cooked meat (outside the home), sugar, and fats, and were associated with increased knowledge of COVID-19. Vitamin C and immunity-boosting supplement consumption were significantly associated with increased knowledge regarding COVID-19 (< 0.05). Inadequate knowledge about COVID-19 and the presence of anxiety and depression were found among most of the study participants. There is a need to conduct educational seminars to limit the health consequences resulting from COVID-19 lockdown.
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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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Differential Health Effects on Inflammatory, Immunological and Stress Parameters in Professional Soccer Players and Sedentary Individuals after Consuming a Synbiotic. A Triple-Blinded, Randomized, Placebo-Controlled Pilot Study.
Quero, CD, Manonelles, P, Fernández, M, Abellán-Aynés, O, López-Plaza, D, Andreu-Caravaca, L, Hinchado, MD, Gálvez, I, Ortega, E
Nutrients. 2021;13(4)
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Synbiotic, a mixture of prebiotics and probiotics, is known to improve neurotransmitter interactions, immune, inflammatory, and stress responses by modulating the gut microbial composition. It is also believed that physical activity plays an important role in the modulation of immune function and stress response. The purpose of this triple-blinded, randomized, placebo-controlled pilot study was to evaluate the health benefits of symbiotic intervention in fourteen sedentary students and thirteen soccer players, especially in terms of improving immunophysiological and metabolic parameters. The 300mg of symbiotic intervention contained Bifidobacterium lactis CBP-001010, Lactobacillus rhamnosus CNCM I-4036, Bifidobacterium longum ES1(109 colony-forming unit), and fructooligosaccharides (200 mg) plus 1.5 mg of zinc, 8.25 µg of selenium, 0.75 µg of vitamin, and maltodextrin. Following a one-month intervention with synbiotic formulation, soccer players showed improvements in anxiety, sleep quality and stress, a slight reduction in proinflammatory cytokine IL-1β, an exercise-induced significant increase in dopamine and a slight elevation of corticotropin-releasing hormone. For confirmation of results of this pilot study and to assess more significant effects of symbiotic intervention in athletes as well as in the general population, longer-term robust studies are required. The findings of this study can help healthcare professionals understand the extensive health benefits of synbiotic intervention and its relationship to physical activity.
Abstract
The main objective of this research was to carry out an experimental study, triple-blind, on the possible immunophysiological effects of a nutritional supplement (synbiotic, Gasteel Plus®, Heel España S.A.U.), containing a mixture of probiotic strains, such as Bifidobacterium lactis CBP-001010, Lactobacillus rhamnosus CNCM I-4036, and Bifidobacterium longum ES1, as well as the prebiotic fructooligosaccharides, on both professional athletes and sedentary people. The effects on some inflammatory/immune (IL-1β, IL-10, and immunoglobulin A) and stress (epinephrine, norepinephrine, dopamine, serotonin, corticotropin-releasing hormone (CRH), Adrenocorticotropic hormone (ACTH), and cortisol) biomarkers were evaluated, determined by flow cytometer and ELISA. The effects on metabolic profile and physical activity, as well as on various parameters that could affect physical and mental health, were also evaluated via the use of accelerometry and validated questionnaires. The participants were professional soccer players in the Second Division B of the Spanish League and sedentary students of the same sex and age range. Both study groups were randomly divided into two groups: a control group-administered with placebo, and an experimental group-administered with the synbiotic. Each participant was evaluated at baseline, as well as after the intervention, which lasted one month. Only in the athlete group did the synbiotic intervention clearly improve objective physical activity and sleep quality, as well as perceived general health, stress, and anxiety levels. Furthermore, the synbiotic induced an immunophysiological bioregulatory effect, depending on the basal situation of each experimental group, particularly in the systemic levels of IL-1β (increased significantly only in the sedentary group), CRH (decreased significantly only in the sedentary group), and dopamine (increased significantly only in the athlete group). There were no significant differences between groups in the levels of immunoglobulin A or in the metabolic profile as a result of the intervention. It is concluded that synbiotic nutritional supplements can improve anxiety, stress, and sleep quality, particularly in sportspeople, which appears to be linked to an improved immuno-neuroendocrine response in which IL-1β, CRH, and dopamine are clearly involved.
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How Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Progresses: The Natural History of ME/CFS.
Nacul, L, O'Boyle, S, Palla, L, Nacul, FE, Mudie, K, Kingdon, CC, Cliff, JM, Clark, TG, Dockrell, HM, Lacerda, EM
Frontiers in neurology. 2020;11:826
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A good understanding of the disease course is vital not only for the design of preventative and intervention studies, but also to assess the timing and type of intervention that minimizes disease risk or optimizes prognosis. The aim of this review was to explore the long-term course of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and how presentation and pathophysiological abnormalities may vary with time. Literature shows that it is unknown how the initial host response to a stressor or insult compares in individuals who do or do not develop typical symptoms of ME/CFS. However, the return to good health, following exposure to mild or moderate levels of insult, seems to be impeded in ME/CFS when symptoms persist for longer than 3–6 months. Authors sought to provide a simple framework, similar to those of other chronic diseases, in an effort to extend the temporal perception of ME/CFS and better incorporate the less defined pre-illness stages of the disease. In fact, they conclude that by applying this framework to ME/CFS research efforts could better elucidate the pathophysiological mechanisms of the disease and identify potential therapeutic targets at distinct stages.
Abstract
We propose a framework for understanding and interpreting the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) that considers wider determinants of health and long-term temporal variation in pathophysiological features and disease phenotype throughout the natural history of the disease. As in other chronic diseases, ME/CFS evolves through different stages, from asymptomatic predisposition, progressing to a prodromal stage, and then to symptomatic disease. Disease incidence depends on genetic makeup and environment factors, the exposure to singular or repeated insults, and the nature of the host response. In people who develop ME/CFS, normal homeostatic processes in response to adverse insults may be replaced by aberrant responses leading to dysfunctional states. Thus, the predominantly neuro-immune manifestations, underlined by a hyper-metabolic state, that characterize early disease, may be followed by various processes leading to multi-systemic abnormalities and related symptoms. This abnormal state and the effects of a range of mediators such as products of oxidative and nitrosamine stress, may lead to progressive cell and metabolic dysfunction culminating in a hypometabolic state with low energy production. These processes do not seem to happen uniformly; although a spiraling of progressive inter-related and self-sustaining abnormalities may ensue, reversion to states of milder abnormalities is possible if the host is able to restate responses to improve homeostatic equilibrium. With time variation in disease presentation, no single ME/CFS case description, set of diagnostic criteria, or molecular feature is currently representative of all patients at different disease stages. While acknowledging its limitations due to the incomplete research evidence, we suggest the proposed framework may support future research design and health care interventions for people with ME/CFS.
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Effect of ultra-processed diet on gut microbiota and thus its role in neurodegenerative diseases.
Martínez Leo, EE, Segura Campos, MR
Nutrition (Burbank, Los Angeles County, Calif.). 2020;71:110609
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The consumption of ultra-processed foods has increased dramatically in recent years, resulting in an overconsumption of foods that are nutritionally only suitable to be consumed occasionally. Prolonged and short-term dietary modifications can affect the composition and diversity of the gut microbiota and in turn, dysregulation of the gut microbiota may be associated with diseases of the brain. This systematic review study aimed to determine the relationship between diets high in ultra-processed foods, gut microbiota dysregulation and how this may influence early development of brain diseases. The authors first reviewed literature surrounding the role of gut microbiota on health owing to their ability to produce signalling molecules that have various functions around the body. An imbalance in the gut microbiota can result in an overproduction of signalling molecules that contribute to an unhealthy state. These signalling molecules can also act on the brain through several ways such as the nervous, circulatory, and immune systems. The review demonstrates that high fat, high sugar diets are related to increased risk for diseases such as Alzheimer’s disease and that diets high in fibre, are related to a low incidence of brain disorders, but as very few studies have looked at this in relation to gut microbiota relationships are only speculative. It was concluded that gut microbiota dysregulation could act as a clinical indicator between brain diseases and ultra-processed foods, however further studies are needed on the relationship between diet, gut microbiota and brain diseases.
Abstract
The current dietary pattern is characterized by high consumption of ultra-processed foods and lower consumption of fiber and vegetables, environmental factors that are associated directly with the current incidence of chronic metabolic diseases. Diet is an environmental factor that influences the diversity and functionality of the gut microbiota, where dietary changes have a direct action on their homeostasis. The environment created in the gut by ultra-processed foods, a hallmark of the Western diet that are recognized as trigger factors for low-grade systemic inflammatory and oxidative changes, favor the development of neurodegenerative diseases (NDs). From a systematic search, the present review analyzes the relationship and effect of the current feeding pattern, with the dysregulation of the microbiota and its influence on the development of cognitive decline. Because diagnosis of NDs is usually at late stages, this review highlights the importance of a search for stricter public health strategies regarding access to and development of ultra-processed foods.
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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.