Gut microbiome and the brain

The Microbiome-Gut-Brain Axis in Health and Disease.: Gut microbes are capable of producing most neurotransmitters found in the human brain. Evidence is accumulating to support the view that gut microbes influence central neurochemistry and behavior. Irritable bowel syndrome is regarded as the prototypic disorder of the brain-gut-microbiota axis that can be responsive to probiotic therapy. Translational studies indicate that certain bacteria may have an impact on stress responses and cognitive functioning. Manipulating the gut microbiota with psych

The role of gut dysbiosis in Parkinson's disease: mechanistic insights and therapeutic options.: Parkinson's disease is a common neurodegenerative disorder in which gastrointestinal symptoms may appear prior to motor symptoms. The gut microbiota of patients with Parkinson's disease shows unique changes, which may be used as early biomarkers of disease. Alterations in the gut microbiota composition may be related to the cause or effect of motor or non-motor symptoms, but the specific pathogenic mechanisms are unclear. The gut microbiota and its metabolites have been suggested to be involved

How Microbes Affect Depression: Underlying Mechanisms via the Gut-Brain Axis and the Modulating Role of Probiotics.: Accumulating evidence suggests that the gut microbiome influences the brain functions and psychological state of its host via the gut-brain axis, and gut dysbiosis has been linked to several mental illnesses, including major depressive disorder (MDD). Animal experiments have shown that a depletion of the gut microbiota leads to behavioral changes, and is associated with pathological changes, including abnormal stress response and impaired adult neurogenesis. Short-chain fatty acids such as butyr

The Microbiota-Gut-Brain Axis.: The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biological and physiological basis of psychiatric, neurodevelopmental, age

Psychological comorbidity in gastrointestinal diseases: Update on the brain-gut-microbiome axis.: The high comorbidity of psychological disorders in both functional and organic gastrointestinal diseases suggests the intimate and complex link between the brain and the gut. Termed the brain-gut axis, this bidirectional communication between the central nervous system and enteric nervous system relies on immune, endocrine, neural, and metabolic pathways. There is increasing evidence that the gut microbiome is a key part of this system, and dysregulation of the brain-gut-microbiome axis (BGMA) h

Probiotics and fructo-oligosaccharide intervention modulate the microbiota-gut brain axis to improve autism spectrum reducing also the hyper-serotonergic state and the dopamine metabolism disorder.: The prevalence of autism spectrum disorders (ASD) is increasing, but its etiology remains elusive and hence an effective treatment is not available. Previous research conducted on animal models suggests that microbiota-gut-brain axis may contribute to ASD pathology and more human research is needed. This study was divided into two stages,.At the discovery stage, we compared the differences in gut microbiota profiles (using 16S rRNA sequencing), fecal SCFAs (using GC-MS) and plasma neurotransmitt

Health relevance of the modification of low grade inflammation in ageing (inflammageing) and the role of nutrition.

Ageing of the global population has become a public health concern with an important socio-economic dimension. Ageing is characterized by an increase in the concentration of inflammatory markers in the bloodstream, a phenomenon that has been termed "inflammageing". The inflammatory response is beneficial as an acute, transient reaction to harmful conditions, facilitating the defense, repair, turnover and adaptation of many tissues. However, chronic and low grade inflammation is likely to be detrimental for many tissues and for normal functions. We provide an overview of low grade inflammation (LGI) and determine the potential drivers and the effects of the "inflamed" phenotype observed in the elderly. We discuss the role of gut microbiota and immune system crosstalk and the gut-brain axis. Then, we focus on major health complications associated with LGI in the elderly, including mental h…

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Sex hormones in the modulation of irritable bowel syndrome.

Compelling evidence indicates sex and gender differences in epidemiology, symptomatology, pathophysiology, and treatment outcome in irritable bowel syndrome (IBS). Based on the female predominance as well as the correlation between IBS symptoms and hormonal status, several models have been proposed to examine the role of sex hormones in gastrointestinal (GI) function including differences in GI symptoms expression in distinct phases of the menstrual cycle, in pre- and post-menopausal women, during pregnancy, hormonal treatment or after oophorectomy. Sex hormones may influence peripheral and central regulatory mechanisms of the brain-gut axis involved in the pathophysiology of IBS contributing to the alterations in visceral sensitivity, motility, intestinal barrier function, and immune activation of intestinal mucosa. Sex differences in stress response of the hypothalamic-pituitary-adrena…

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Kynurenines: Tryptophan's metabolites in exercise, inflammation, and mental health.

Kynurenine metabolites are generated by tryptophan catabolism and regulate biological processes that include host-microbiome signaling, immune cell response, and neuronal excitability. Enzymes of the kynurenine pathway are expressed in different tissues and cell types throughout the body and are regulated by cues, including nutritional and inflammatory signals. As a consequence of this systemic metabolic integration, peripheral inflammation can contribute to accumulation of kynurenine in the brain, which has been associated with depression and schizophrenia. Conversely, kynurenine accumulation can be suppressed by activating kynurenine clearance in exercised skeletal muscle. The effect of exercise training on depression through modulation of the kynurenine pathway highlights an important mechanism of interorgan cross-talk mediated by these metabolites. Here, we discuss peripheral mechani…

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Microbiota-Brain-Gut Axis and Neurodegenerative Diseases.

Purpose of review: The purposes of this review were as follows: first, to provide an overview of the gut microbiota and its interactions with the gut and the central nervous system (the microbiota-gut-brain axis) in health, second, to review the relevance of this axis to the pathogenesis of neurodegenerative diseases, such as Parkinson's disease, and, finally, to assess the potential for microbiota-targeted therapies. Recent findings: Work on animal models has established the microbiota-gut-brain axis as a real phenomenon; to date, the evidence for its operation in man has been limited and has been confronted by considerable logistical challenges. Animal and translational models have incriminated a disturbed gut microbiota in a number of CNS disorders, including Parkinson's disease; data from human studies is scanty. While a theoretical basis can be developed for the use of microbiota-di…

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Gut microbiome signatures reflect different subtypes of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a heterogeneous condition with multifactorial pathogenesis. We studied deeply phenotyped individuals with microbiota sequencing enrolled in the American Gut Project. The IBS subjects were matched by age, gender, body mass index, geography, and dietary patterns with non-IBS controls. A total of 942 subjects with IBS-Diarrhea (IBS-D), IBS-Constipation (IBS-C), unclassified IBS (IBS-U), and 942 non-IBS controls were included. We compared taxonomic and functional composition of gut microbiota based on 16S sequencing data and linked them with clinical characteristics and dietary factors. Subjects with IBS-D or IBS-U but not IBS-C showed significantly reduced bacterial diversity (Shannon; p < .01). Distinct bacterial signatures were associated with different IBS subtypes, and the related functional changes were related to IBS pathogenesis, such as the increase…

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Impact of traditional Chinese medicine treatment on chronic unpredictable mild stress-induced depression-like behaviors: intestinal microbiota and gut microbiome function.

Gut microbiota dysbiosis is a recognized contributing factor to many noncommunicable diseases, but more evidence is still needed to illustrate its causative impact on mental and brain health disorders and mechanism(s) for targeted mitigation. Traditional Chinese Medicine (TCM) has been used in the management of neuropsychiatric diseases for many years in China. In this study, a randomized, controlled trial was conducted to examine the impact of stress on gut microbiota dysbiosis and depression, and TCM in alleviating the damage using Chronic Unpredictable Mild Stress (CUMS) rats, a well-established rodent model for depression. The behaviors of rats and the profiles of the fecal microbiota were assessed by an array of behavioral tests and 16S rRNA gene sequencing, and the intestinal microbial function was assessed by shotgun sequencing-based metagenomic analysis of microbial DNA from feca…

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Impact of beneficial bacteria supplementation on the gut microbiota, colony development and productivity of Apis mellifera L.

Honey bees are important pollinators of several crops and ecosystems, having a great ecological and economic value. In Europe, the restricted use of chemicals and therapeutic agents in the beekeeping sector has stimulated the search for natural alternatives with a special focus on gut symbionts. The modulation of the gut microbiota has been recognised as a practical and successful approach in the entomological field for the management of insect-related problems. To date, only a few studies have investigated the effect of bacterial supplementation on the health status of colonies, colony productivity and gut symbionts. To this purpose, a preparation of sugar syrup containing bifidobacteria and lactobacilli isolated from bee gut was sprayed on the frames of an apiary located in open field once a week for four weeks. Treated and control hives were monitored for two months for brood extensio…

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Microbiota and host determinants of behavioural phenotype in maternally separated mice.

Early-life stress is a determinant of vulnerability to a variety of disorders that include dysfunction of the brain and gut. Here we exploit a model of early-life stress, maternal separation (MS) in mice, to investigate the role of the intestinal microbiota in the development of impaired gut function and altered behaviour later in life. Using germ-free and specific pathogen-free mice, we demonstrate that MS alters the hypothalamic-pituitary-adrenal axis and colonic cholinergic neural regulation in a microbiota-independent fashion. However, microbiota is required for the induction of anxiety-like behaviour and behavioural despair. Colonization of adult germ-free MS and control mice with the same microbiota produces distinct microbial profiles, which are associated with altered behaviour in MS, but not in control mice. These results indicate that MS-induced changes in host physiology lead …

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Signaling inflammation across the gut-brain axis.

The brain and gastrointestinal tract are critical sensory organs responsible for detecting, relaying, integrating, and responding to signals derived from the internal and external environment. At the interface of this sensory function, immune cells in the intestines and brain consistently survey environmental factors, eliciting responses that inform on the physiological state of the body. Recent research reveals that cross-talk along the gut-brain axis regulates inflammatory nociception, inflammatory responses, and immune homeostasis. Here, we discuss molecular and cellular mechanisms involved in the signaling of inflammation across the gut-brain axis. We further highlight interactions between the gut and the brain in inflammation-associated diseases.

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Microbiome-microglia connections via the gut-brain axis.

Microglia, the resident immune cells in the brain, are essential for modulating neurogenesis, influencing synaptic remodeling, and regulating neuroinflammation by surveying the brain microenvironment. Microglial dysfunction has been implicated in the onset and progression of several neurodevelopmental and neurodegenerative diseases; however, the multitude of factors and signals influencing microglial activity have not been fully elucidated. Microglia not only respond to local signals within the brain but also receive input from the periphery, including the gastrointestinal (GI) tract. Recent preclinical findings suggest that the gut microbiome plays a pivotal role in regulating microglial maturation and function, and altered microbial community composition has been reported in neurological disorders with known microglial involvement in humans. Collectively, these findings suggest that bi…

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Why does the microbiome affect behaviour?

Growing evidence indicates that the mammalian microbiome can affect behaviour, and several symbionts even produce neurotransmitters. One common explanation for these observations is that symbionts have evolved to manipulate host behaviour for their benefit. Here, we evaluate the manipulation hypothesis by applying evolutionary theory to recent work on the gut-brain axis. Although the theory predicts manipulation by symbionts under certain conditions, these appear rarely satisfied by the genetically diverse communities of the mammalian microbiome. Specifically, any symbiont investing its resources to manipulate host behaviour is expected to be outcompeted within the microbiome by strains that do not manipulate and redirect their resources into growth and survival. Moreover, current data provide no clear evidence for manipulation. Instead, we show how behavioural effects can readily arise …

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A randomized controlled trial into the effects of probiotics on electroencephalography in preschoolers with autism.

Lay abstract: This study investigates the effects of a probiotic on preschoolers' brain electrical activity with autism spectrum disorder. Autism is a disorder with an increasing prevalence characterized by an enormous individual, family, and social cost. Although the etiology of autism spectrum disorder is unknown, an interaction between genetic and environmental factors is implicated, converging in altered brain synaptogenesis and, therefore, connectivity. Besides deepening the knowledge on the resting brain electrical activity that characterizes this disorder, this study allows analyzing the positive central effects of a 6-month therapy with a probiotic through a randomized, double-blind placebo-controlled study and the correlations between electroencephalography activity and biochemical and clinical parameters. In subjects treated with probiotics, we observed a decrease of power in f…

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Probiotic Bifidobacterium breve in Improving Cognitive Functions of Older Adults with Suspected Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Probiotics use has been associated with modulation of inflammation and considered as a possible intervention for CNS diseases such as mild cognitive impairment (MCI) and dementia. Objective: We aimed to test the effect of the probiotic strain, Bifidobacterium breve A1 (MCC1274), to restore cognition in a physically healthy, suspected MCI population. Methods: In this randomized, double-blind, placebo-controlled trial, 80 healthy older adults suffering from MCI were divided into two even groups to receive once daily either probiotic (B. breve A1, 2×1010 CFU) or placebo for 16 weeks using a computer-generated algorithm. Cognitive functions were assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Japanese version of the MCI Screen (JMCIS) tests before and after the study as primary and secondary endpoints, respectively. Results: 79 p…

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Vitamin D and probiotic co-supplementation affects mental health, hormonal, inflammatory and oxidative stress parameters in women with polycystic ovary syndrome.

Objective: The aim of this study was to determine the effect of vitamin D and probiotic co-administration on mental health, hormonal, inflammatory and oxidative stress parameters in women with polycystic ovary syndrome (PCOS). Methods: This randomized, double-blinded, placebo-controlled clinical trial was carried out on 60 subjects, aged 18-40 years old. Subjects were randomly allocated to take either 50,000 IU vitamin D every 2 weeks plus 8 × 109 CFU/day probiotic (n = 30) or placebo (n = 30) for 12 weeks. Results: Vitamin D and probiotic co-supplementation, compared with the placebo, significantly improved beck depression inventory [β (difference in the mean of outcomes measures between treatment groups) - 0.58; 95% CI, - 1.15, - 0.02; P = 0.04], general health questionnaire scores (β - 0.93; 95% CI, - 1.78, - 0.08; P = 0.03) and depression, anxiety and stress scale scores (β - 0.90; 9…

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Influence of 4-week multi-strain probiotic administration on resting-state functional connectivity in healthy volunteers.

Purpose: Experimental investigations in rodents have contributed significantly to our current understanding of the potential importance of the gut microbiome and brain interactions for neurotransmitter expression, neurodevelopment, and behaviour. However, clinical evidence to support such interactions is still scarce. The present study used a double-blind, randomized, pre- and post-intervention assessment design to investigate the effects of a 4-week multi-strain probiotic administration on whole-brain functional and structural connectivity in healthy volunteers. Methods: Forty-five healthy volunteers were recruited for this study and were divided equally into three groups (PRP: probiotic, PLP: placebo, and CON: control). All the participants underwent resting-state functional MRI and diffusion MRI brain scans twice during the course of study, at the beginning (time point 1) and after 4 …

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The effects of vitamin D and probiotic co-supplementation on mental health parameters and metabolic status in type 2 diabetic patients with coronary heart disease: A randomized, double-blind, placebo-controlled trial.

Background: This study was carried out to evaluate the effects of vitamin D and probiotic co-supplementation on mental health parameters and metabolic status in diabetic people with coronary heart disease (CHD). Methods: This randomized, double-blind, placebo-controlled trial was carried out among 60 diabetic people with CHD, aged 45-85 years old. Subjects were randomly allocated into two groups to receive either 50,000 IU vitamin D every 2 weeks plus 8 × 109 CFU/g probiotic of Lactocare Zisttakhmir Co (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were obtained at baseline and after the 12-week intervention to determine metabolic profiles. Results: After the 12-week intervention, compared with the placebo, vitamin D and probiotic co-supplementation resulted in significant improvements in beck depression inventory total score (-2.8 ± 3.8 vs. -0.9 ± 2.1, P = 0.01), beck …

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Effect of Lactobacillus rhamnosus HN001 in Pregnancy on Postpartum Symptoms of Depression and Anxiety: A Randomised Double-blind Placebo-controlled Trial.

Background: Probiotics may help to prevent symptoms of anxiety and depression through several putative mechanisms. Objective: The aim of this study was to evaluate the effect of Lactobacillus rhamnosus HN001 (HN001) given in pregnancy and postpartum on symptoms of maternal depression and anxiety in the postpartum period. This was a secondary outcome, the primary outcome being eczema in the offspring at 12months of age. Design, setting, participants: A randomised, double-blind, placebo-controlled trial of the effect of HN001 on postnatal mood was conducted in 423 women in Auckland and Wellington, New Zealand. Women were recruited at 14-16weeks gestation. Intervention: Women were randomised to receive either placebo or HN001 daily from enrolment until 6months postpartum if breastfeeding. Outcome measures: Modified versions of the Edinburgh Postnatal Depression Scale and State Trait Anxiety…

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Clinical and metabolic response to probiotic administration in patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial.

Objective: We are aware of no study examining the effects of probiotic supplementation on symptoms of depression, metabolic profiles, serum high-sensitivity C-reactive protein (hs-CRP), and biomarkers of oxidative stress in patients with major depressive disorder (MDD). The present study was designed to determine the effects of probiotic intake on symptoms of depression and metabolic status in patients with MDD. Methods: This randomized, double-blind, placebo-controlled clinical trial included 40 patients with a diagnosis of MDD based on DSM-IV criteria whose age ranged between 20 and 55 y. Patients were randomly allocated into two groups to receive either probiotic supplements (n = 20) or placebo (n = 20) for 8 wk. Probiotic capsule consisted of three viable and freeze-dried strains: Lactobacillus acidophilus (2 × 10(9) CFU/g), Lactobacillus casei (2 × 10(9) CFU/g), and Bifidobacterium …

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Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers.

The emerging concept of psychobiotics-live microorganisms with a potential mental health benefit-represents a novel approach for the management of stress-related conditions. The majority of studies have focused on animal models. Recent preclinical studies have identified the B. longum 1714 strain as a putative psychobiotic with an impact on stress-related behaviors, physiology and cognitive performance. Whether such preclinical effects could be translated to healthy human volunteers remains unknown. We tested whether psychobiotic consumption could affect the stress response, cognition and brain activity patterns. In a within-participants design, healthy volunteers (N=22) completed cognitive assessments, resting electroencephalography and were exposed to a socially evaluated cold pressor test at baseline, post-placebo and post-psychobiotic. Increases in cortisol output and subjective anxi…

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Bifidobacterium adolescentis as a key member of the human gut microbiota in the production of GABA.

Gamma aminobutyric acid (GABA) is the principal inhibitory neurotransmitter playing a key role in anxiety and depression disorders in mammals. Recent studies revealed that members of the gut microbiota are able to produce GABA modulating the gut-brain axis response. Among members of the human gut microbiota, bifidobacteria are well known to establish many metabolic and physiologic interactions with the host. In this study, we performed genome analyses of more than 1,000 bifidobacterial strains publicly available revealing that Bifidobacterium adolescentis taxon might represent a model GABA producer in human gastrointestinal tract. Moreover, the in silico screening of human/animal metagenomic datasets showed an intriguing association/correlation between B. adolescentis load and mental disorders such as depression and anxiety. Interestingly, in vitro screening of 82 B. adolescentis strains…

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Whole-grain wheat consumption reduces inflammation in a randomized controlled trial on overweight and obese subjects with unhealthy dietary and lifestyle behaviors: role of polyphenols bound to cereal dietary fiber.

Background: Epidemiology associates whole-grain (WG) consumption with several health benefits. Mounting evidence suggests that WG wheat polyphenols play a role in mechanisms underlying health benefits. Objective: The objective was to assess circulating concentration, excretion, and the physiologic role of WG wheat polyphenols in subjects with suboptimal dietary and lifestyle behaviors. Design: A placebo-controlled, parallel-group randomized trial with 80 healthy overweight/obese subjects with low intake of fruit and vegetables and sedentary lifestyle was performed. Participants replaced precise portions of refined wheat (RW) with a fixed amount of selected WG wheat or RW products for 8 wk. At baseline and every 4 wk, blood, urine, feces, and anthropometric and body composition measures were collected. Profiles of phenolic acids in biological samples, plasma markers of metabolic disease a…

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Psychoneuroimmunological approach to gastrointestinal related pain.

Background and purpose (aims): Psychoneuroimmunology is both a theoretical and practical field of medicine in which human biology and psychology are considered an interconnected unity. Through such a framework it is possible to elucidate complex syndromes in gastrointestinal related pain, particularly chronic non-malignant. The aim is to provide insight into pathophysiological mechanisms and suggest treatment modalities according to a comprehensive paradigm. The article also presents novel findings that may guide clinicians to recognize new targets or scientists to find new research topics. Methods: A literature search of 'PubMed' and 'Google Scholar' databases was performed. Search terms included: 'Visceral pain', 'Psychoneuroimmunology', 'Psychoneuroimmunology and pain', 'Pain in GI system', 'GI related pain', 'Pain and microbiota', 'Enteric nervous system', 'Enteric nervous system and…

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Effects of multimodal prehabilitation and exercise prehabilitation on patients undergoing colorectal surgery: A systematic review and meta-analysis of randomised controlled trials.

Background: Multimodal prehabilitation and exercise prehabilitation are important processes for patients undergoing colorectal surgery. There are no reviews simultaneously analysing the effects of both types of prehabilitation for patients undergoing colorectal surgery. Methods: We searched PubMed, Embase, Scopus, Web of Science, the Cochrane Library, ProQuest, and CINAHL Plus with Full Text for relevant randomised controlled trials on multimodal prehabilitation and exercise prehabilitation. The primary outcomes in our meta-analysis were functional capacity, hospital length of stay, postoperative complications, anxiety, and depression scores. Results: We included 17 studies involving 1961 for colorectal surgery patients. The results of the meta-analysis suggested that multimodal prehabilitation could improve functional capacity (the 6-minute walk test) in patients undergoing colorectal s…

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The serotonin theory of depression: a systematic umbrella review of the evidence.

The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity in a systematic umbrella review of the principal relevant areas of research. PubMed, EMBASE and PsycINFO were searched using terms appropriate to each area of research, from their inception until December 2020. Systematic reviews, meta-analyses and large data-set analyses in the following areas were identified: serotonin and serotonin metabolite, 5-HIAA, concentrations in body fluids; serotonin 5-HT1A receptor binding; serotonin transporter (SERT) levels measured by imaging or at post-mortem; tryptophan depletion studies; SERT gene associations and SERT gene-environment interactions. Studies of depression associated with physical conditions and specific subtypes of depression (e.g. bipolar depression…

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The NASA Twins Study: A multidimensional analysis of a year-long human spaceflight.

To understand the health impact of long-duration spaceflight, one identical twin astronaut was monitored before, during, and after a 1-year mission onboard the International Space Station; his twin served as a genetically matched ground control. Longitudinal assessments identified spaceflight-specific changes, including decreased body mass, telomere elongation, genome instability, carotid artery distension and increased intima-media thickness, altered ocular structure, transcriptional and metabolic changes, DNA methylation changes in immune and oxidative stress-related pathways, gastrointestinal microbiota alterations, and some cognitive decline postflight. Although average telomere length, global gene expression, and microbiome changes returned to near preflight levels within 6 months after return to Earth, increased numbers of short telomeres were observed and expression of some genes …

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