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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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Probiotics, Prebiotics and Postbiotics on Mitigation of Depression Symptoms: Modulation of the Brain-Gut-Microbiome Axis.
Chudzik, A, Orzyłowska, A, Rola, R, Stanisz, GJ
Biomolecules. 2021;11(7)
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The bidirectional communication pathway between the gut microbiota and the central nervous system has been termed the brain-gut-microbiome axis. Increased investigation of this pathway has found the gut bacteria to impact metabolism and the brain, suggesting that modulating the microbiome may elicit change in mental health. The aim of this review is to discuss the current findings in both animal and human studies regarding the use of pro-, pre- and post-biotics in the prevention and treatment of depressive disorders. Studies show that modulating the bacteria in the gut may reduce inflammation, decrease stress hormone levels and adjust the levels of neurotransmitters in the brain. These changes consequently lead to the reduction of depressive symptoms and improvement in mood. While these results are promising, larger clinical trials are needed that include biochemical measurements and fecal microbiome analysis in addition to validated questionnaires. With this in mind, the authors conclude there is huge potential in the role of nutrition as a therapeutic target for neurological and mental health conditions.
Abstract
The brain-gut-microbiome axis is a bidirectional communication pathway between the gut microbiota and the central nervous system. The growing interest in the gut microbiota and mechanisms of its interaction with the brain has contributed to the considerable attention given to the potential use of probiotics, prebiotics and postbiotics in the prevention and treatment of depressive disorders. This review discusses the up-to-date findings in preclinical and clinical trials regarding the use of pro-, pre- and postbiotics in depressive disorders. Studies in rodent models of depression show that some of them inhibit inflammation, decrease corticosterone level and change the level of neurometabolites, which consequently lead to mitigation of the symptoms of depression. Moreover, certain clinical studies have indicated improvement in mood as well as changes in biochemical parameters in patients suffering from depressive disorders.
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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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Effects of Probiotic NVP-1704 on Mental Health and Sleep in Healthy Adults: An 8-Week Randomized, Double-Blind, Placebo-Controlled Trial.
Lee, HJ, Hong, JK, Kim, JK, Kim, DH, Jang, SW, Han, SW, Yoon, IY
Nutrients. 2021;13(8)
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Dietary changes directly alter the gut microbiome composition. A diversified gut microbiome may have therapeutic implications for mental health, and specific strains of probiotics have shown the potential to treat depression and anxiety. Several preclinical trials have found the probiotic mixture NVP-1704 to alleviate depression and anxiety in mice through modulating the gut-brain-microbiome axis. The aim of this randomised, double-blind, placebo-controlled, parallel study was to examine the efficacy and safety of NVP-1704 for the management of depression, anxiety and insomnia in healthy adults. A total of 156 healthy adults with subclinical depression, anxiety and insomnia were randomised to receive either NVP-1704 or placebo for eight weeks. Participants completed various questionnaires and biomarkers of stress and inflammation were assessed. After eight weeks, this study found that NVP-1704 to be a safe and well-tolerated probiotic with beneficial effects on depression, sleep quality, inflammation and gut microbiome composition in healthy adults. Based on this study, the authors conclude the therapeutic effects of NVP-1704 previously found in preclinical mice trials may now be translated to clinical trials. The authors suggest large, highly controlled, longitudinal human studies be conducted in the future to further confirm the benefits of probiotics on mental health and sleep.
Abstract
The human gut microbiome is closely linked to mental health and sleep. We aimed to verify the efficacy and safety of probiotic NVP-1704, a mixture of Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98, in improving stress, depression, anxiety, and sleep disturbances, along with the measurement of some blood biomarkers. A total of 156 healthy adults with subclinical symptoms of depression, anxiety, and insomnia were retrospectively registered and randomly assigned to receive either NVP-1704 (n = 78) or a placebo (n = 78) for eight weeks. Participants completed the Stress Response Inventory, Beck's Depression and Anxiety Inventory, Pittsburg Sleep Quality Index, and Insomnia Severity Index at baseline, at four and eight weeks of treatment. Pre- and post-treatment blood tests for biomarkers were conducted. After intervention, gut microbiota composition was quantified by pyrosequencing the bacterial 16S rRNA gene. The NVP-1704 group had a more significant reduction in depressive symptoms at four and eight weeks of treatment, and anxiety symptoms at four weeks compared to the placebo group. Those receiving NVP-1704 also experienced an improvement in sleep quality. NVP-1704 treatment led to a decrease in serum interleukin-6 levels. Furthermore, NVP-1704 increased Bifidobacteriaceae and Lactobacillacea, whereas it decreased Enterobacteriaceae in the gut microbiota composition. Our findings suggest that probiotic NVP-1704 could be beneficial for mental health and sleep.
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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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Altered Composition of Gut Microbiota in Depression: A Systematic Review.
Barandouzi, ZA, Starkweather, AR, Henderson, WA, Gyamfi, A, Cong, XS
Frontiers in psychiatry. 2020;11:541
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The brain-gut microbiome axis has emerged to be a link between gut microbiota pattern and depression, however the mechanism by which gut microbiota modulate depression-like behaviors remains inconclusive. While studies have observed differences in the diversity and abundance of different bacteria taxa, no definitive classifications have been confirmed. The aim of this systematic review was to identify gut microbiota patterns in people with depression compared with healthy controls. According to the nine articles included in this review, conflicting results were found on characteristics of gut microbiota in people with depression compared to healthy controls. Based on these findings, the authors conclude the role of the microbiota in the development or maintenance of depression remains limited, suggesting the likelihood of confounding factors. Further research is recommended to better understand the relationship between gut microbiota pattern and treatment outcomes for people with depression.
Abstract
Cumulative evidence shows a linkage between gut microbiota pattern and depression through the brain-gut microbiome axis. The aim of this systematic review was to identify the alterations of the gut microbiota patterns in people with depression compared to healthy controls. A comprehensive literature search of human studies, published between January 2000 and June 2019, was reviewed. The key words included gastrointestinal microbiome, gut microbiome, microbiota, depression, depressive symptoms, and depressive disorder. The systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Nine articles met the eligibility criteria. Disparities in α-diversity and β-diversity of the microbiota existed in people with depression compared to healthy controls. At the phylum level, there were inconsistencies in the abundance of Firmicutes, Bacteroidetes, and Proteobacteria. However, high abundance in Actinobacteria and Fusobacteria phyla were observed in people with depression. On the family level, high abundance of Actinomycineae, Coriobacterineae, Bifidobacteriaceae, Clostridiales incertae sedis XI, Porphyromonadaceae, Clostridiaceae, Lactobacillaceae, Streptococcaceae, Eubacteriaceae, Thermoanaerobacteriaceae, Fusobacteriaceae, Nocardiaceae, Streptomycetaceae, and low abundance of Veillonellaceae, Prevotellaceae, Bacteroidaceae, Sutterellaceae, Oscillospiraceae, Marniabilaceae, and Chitinophagaceae were observed in people with depression. On the genus level, high abundance of Oscillibacter, Blautia, Holdemania, Clostridium XIX, Anaerostipes, Anaerofilum, Streptococcus, Gelria, Turicibacter, Parabacteroides, Eggerthella, Klebsiella, Paraprevotella, Veillonella, Clostridium IV, Erysipelotrichaceae incertae sedis, Eubacterium, Parvimonas, Desulfovibrio, Parasutterella, Actinomyces, Asaccharobacter, Atopobium, Olsenella and low abundance of Coprococcus, Lactobacillus, Escherichia/Shigella, Clostridium XlVa, Dialister, Howardella, Pyramidobacter, and Sutterella were found in people with depression. Alteration of gut microbiome patterns was evident in people with depression. Further evidence is warranted to allow for the translation of microbiome findings toward innovative clinical strategies that may improve treatment outcomes in people with depression.
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Possible long-term endocrine-metabolic complications in COVID-19: lesson from the SARS model.
Mongioì, LM, Barbagallo, F, Condorelli, RA, Cannarella, R, Aversa, A, La Vignera, S, Calogero, AE
Endocrine. 2020;68(3):467-470
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Coronavirus disease 2019 (Covid-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Little is known about how it affects the endocrine system and it is likely that some patients who have recovered may suffer long-term consequences. The severe acute respiratory syndrome coronavirus (SARS-CoV) that caused the SARS outbreak in 2003 has many similarities. This editorial looks at the possible effects on the endocrine system of SARS-CoV-2 by looking at the long-term effects seen in SARS. In the case of SARS-CoV, it was thought that the virus could directly damage pancreatic cells leading to type 2 diabetes. It is hypothesized that Covid-19 patients could develop this condition by the same mechanism. Although no study on SARS reported the link between obesity and higher mortality rate, there is evidence that obese Covid-19 patients have worse clinical outcomes. There is no data yet for Covid-19, but adrenal insufficiency and impaired thyroid function were shown in some cases of SARS. To identify and treat any possible long-term effects of Covid-19, endocrinologists should monitor hormone levels and metabolic functions.
Abstract
The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is centralizing the interest of the scientific world. In the next months, long-term consequences on the endocrine system may arise following COVID-19. In this article, we hypothesized the effects of SARS-CoV-2 taking into account what learned from the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused SARS in 2003.
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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.