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

May the Force Be With You: The Light and Dark Sides of the Microbiota-Gut-Brain Axis in Neuropsychiatry.

The role of the gut microbiota in health and disease is becoming increasingly recognized. The microbiota-gut-brain axis is a bi-directional pathway between the brain and the gastrointestinal system. The bacterial commensals in our gut can signal to the brain through a variety of mechanisms, which are slowly being resolved. These include the vagus nerve, immune mediators and microbial metabolites, which influence central processes such as neurotransmission and behaviour. Dysregulation in the composition of the gut microbiota has been identified in several neuropsychiatric disorders, such as autism, schizophrenia and depression. Moreover, preclinical studies suggest that they may be the driving force behind the behavioural abnormalities observed in these conditions. Understanding how bacterial commensals are involved in regulating brain function may lead to novel strategies for development…

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Psychobiotics: a novel class of psychotropic.

Here, we define a psychobiotic as a live organism that, when ingested in adequate amounts, produces a health benefit in patients suffering from psychiatric illness. As a class of probiotic, these bacteria are capable of producing and delivering neuroactive substances such as gamma-aminobutyric acid and serotonin, which act on the brain-gut axis. Preclinical evaluation in rodents suggests that certain psychobiotics possess antidepressant or anxiolytic activity. Effects may be mediated via the vagus nerve, spinal cord, or neuroendocrine systems. So far, psychobiotics have been most extensively studied in a liaison psychiatric setting in patients with irritable bowel syndrome, where positive benefits have been reported for a number of organisms including Bifidobacterium infantis. Evidence is emerging of benefits in alleviating symptoms of depression and in chronic fatigue syndrome. Such ben…

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The gut microbiota-brain axis in behaviour and brain disorders.

In a striking display of trans-kingdom symbiosis, gut bacteria cooperate with their animal hosts to regulate the development and function of the immune, metabolic and nervous systems through dynamic bidirectional communication along the 'gut-brain axis'. These processes may affect human health, as certain animal behaviours appear to correlate with the composition of gut bacteria, and disruptions in microbial communities have been implicated in several neurological disorders. Most insights about host-microbiota interactions come from animal models, which represent crucial tools for studying the various pathways linking the gut and the brain. However, there are complexities and manifest limitations inherent in translating complex human disease to reductionist animal models. In this Review, we discuss emerging and exciting evidence of intricate and crucial connections between the gut microb…

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Tryptophan Metabolism: A Link Between the Gut Microbiota and Brain.

The gut-brain axis (GBA) is a bilateral communication network between the gastrointestinal (GI) tract and the central nervous system. The essential amino acid tryptophan contributes to the normal growth and health of both animals and humans and, importantly, exerts modulatory functions at multiple levels of the GBA. Tryptophan is the sole precursor of serotonin, which is a key monoamine neurotransmitter participating in the modulation of central neurotransmission and enteric physiological function. In addition, tryptophan can be metabolized into kynurenine, tryptamine, and indole, thereby modulating neuroendocrine and intestinal immune responses. The gut microbial influence on tryptophan metabolism emerges as an important driving force in modulating tryptophan metabolism. Here, we focus on the potential role of tryptophan metabolism in the modulation of brain function by the gut microbio…

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Small talk: microbial metabolites involved in the signaling from microbiota to brain.

The wealth of biotransformational capabilities encoded in the microbiome expose the host to an array of bioactive xenobiotic products. Several of these metabolites participate in the communication between the gastrointestinal tract and the central nervous system and have potential to modulate central physiological and pathological processes. This biochemical interplay can occur through various direct and indirect mechanisms. These include binding to host receptors in the brain, stimulation of the vagus nerve in the gut, alteration of central neurotransmission, and modulation of neuroinflammation. Here, the potential for short chain fatty acids, bile acids, neurotransmitters and other bioactive products of the microbiome to participate in the gut-brain axis will be reviewed.

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Gut Microbiota-brain Axis.

Objective: To systematically review the updated information about the gut microbiota-brain axis. Data sources: All articles about gut microbiota-brain axis published up to July 18, 2016, were identified through a literature search on PubMed, ScienceDirect, and Web of Science, with the keywords of "gut microbiota", "gut-brain axis", and "neuroscience". Study selection: All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed, with no limitation of study design. Results: It is well-recognized that gut microbiota affects the brain's physiological, behavioral, and cognitive functions although its precise mechanism has not yet been fully understood. Gut microbiota-brain axis may include gut microbiota and their metabolic products, enteric nervous system, sympathetic and parasympathetic branches within the autonomic nervous system, neural-immune system, n…

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Effect of combined bifidobacteria supplementation and resistance training on cognitive function, body composition and bowel habits of healthy elderly subjects.

Physical exercise exerts favourable effects on brain health and quality of life of the elderly; some of these positive health effects are induced by the modulation of microbiota composition. We therefore conducted a randomised, double blind, placebo-controlled trial that assessed whether a combination of Bifidobacterium spp. supplementation and moderate resistance training improved the cognitive function and other health-related parameters in healthy elderly subjects. Over a 12-week period, 38 participants (66-78 years) underwent resistance training and were assigned to the probiotic Bifidobacterium supplementation (n=20; 1.25×1010 cfu each of Bifidobacterium longum subsp. longum BB536, B. longum subsp. infantis M-63, Bifidobacterium breve M-16V and B. breve B-3) or the placebo (n=18) group. At baseline and at 12 weeks, we assessed the cognitive function, using the Japanese version of th…

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A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood.

Background: Recent insights into the role of the human microbiota in cognitive and affective functioning have led to the hypothesis that probiotic supplementation may act as an adjuvant strategy to ameliorate or prevent depression. Objective: Heightened cognitive reactivity to normal, transient changes in sad mood is an established marker of vulnerability to depression and is considered an important target for interventions. The present study aimed to test if a multispecies probiotic containing Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, and Lactococcus lactis (W19 and W58) may reduce cognitive reactivity in non-depressed individuals. Design: In a triple-blind, placebo-controlled, randomized, pre- and post-intervention assessment design, 20 healthy participants wit…

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Efficacy of probiotics on cognition, and biomarkers of inflammation and oxidative stress in adults with Alzheimer's disease or mild cognitive impairment - a meta-analysis of randomized controlled trials.

Probiotics are live microbes that confer health benefits to the host. Preliminary animal evidence supports the potential role of probiotics in ameliorating cognitive health, however, findings from clinical trials in Alzheimer's disease (AD) or mild cognitive impairment (MCI) subjects are controversial. Thus, a meta-analysis is needed to clarify the efficacy of probiotics on cognition in AD or MCI patients. EMBASE, PubMed, Web of Science and Cochrane library were systematically searched and manually screened for relevant published randomized controlled trials (RCTs). Among the 890 citations identified, 5 studies involving 297 subjects met eligibility. There was a significant improvement in cognition (SMD = 0.37; 95% CI, 0.14, 0.61; P = 0.002; I2 = 24%), while a significant reduction in malondialdehyde (SMD = -0.60; 95% CI, -0.91, -0.28; P = 0.000; I2 = 0.0%) and high-sensitivity C-reactiv…

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Probiotics for the prevention of pediatric antibiotic-associated diarrhea.

Background: Antibiotics alter the microbial balance commonly resulting in antibiotic-associated diarrhea (AAD). Probiotics may prevent AAD via providing gut barrier, restoration of the gut microflora, and other potential mechanisms of action. Objectives: The primary objectives were to assess the efficacy and safety of probiotics (any specified strain or dose) used for the prevention of AAD in children. Search methods: MEDLINE, Embase, CENTRAL, CINAHL, and the Web of Science (inception to 28 May 2018) were searched along with registers including the ISRCTN and Clinicaltrials.gov. We also searched the NICE Evidence Services database as well as reference lists from relevant articles. Selection criteria: Randomized, parallel, controlled trials in children (0 to 18 years) receiving antibiotics, that compare probiotics to placebo, active alternative prophylaxis, or no treatment and measure the…

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Do interventions for mood improve inflammatory biomarkers in inflammatory bowel disease?: a systematic review and meta-analysis.

Background: Psychoneuroimmunological mechanisms and the gut-brain axis appear relevant to disease activity and progression in Inflammatory Bowel Disease (IBD). A recent review showed no effect of psychological therapies on self-reported disease activity in IBD. This meta-analysis aims to establish whether interventions targeting mood outcomes (e.g., depression, anxiety and stress) impact inflammation levels in IBD and possible moderators of these effects. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. We searched five electronic databases and included randomised controlled trials where interventions targeted mood and assessed inflammatory outcomes pre- and post-intervention in adults with IBD. Independent reviewers screened studies, extracted data, and assessed methodological quality. Data were pooled to estimate standar…

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Prevalence of symptoms of anxiety and depression in patients with inflammatory bowel disease: a systematic review and meta-analysis.

Background: Inflammatory bowel disease (IBD) is a lifelong condition with no cure. Patients with IBD might experience symptoms of common mental disorders such as anxiety and depression because of bidirectional communication via the gut-brain axis and chronicity of symptoms, and because of impaired quality of life and reduced social functioning. However, uncertainties remain about the magnitude of this problem. We aimed to assess prevalence of symptoms of anxiety or depression in adult patients with IBD. Methods: In this systematic review and meta-analysis, we searched MEDLINE, Embase, Embase Classic, and PsycINFO for papers published from inception to Sept 30, 2020, reporting observational studies that recruited at least 100 adult patients with IBD and that reported prevalence of symptoms of anxiety or depression according to validated screening instruments. We excluded studies that only…

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Gastrointestinal microbiota in children with autism in Slovakia.

Development of Autism Spectrum Disorders (ASD), including autism, is based on a combination of genetic predisposition and environmental factors. Recent data propose the etiopathogenetic role of intestinal microflora in autism. The aim of this study was to elucidate changes in fecal microbiota in children with autism and determine its role in the development of often present gastrointestinal (GI) disorders and possibly other manifestations of autism in Slovakia. The fecal microflora of 10 children with autism, 9 siblings and 10 healthy children was investigated by real-time PCR. The fecal microbiota of autistic children showed a significant decrease of the Bacteroidetes/Firmicutes ratio and elevation of the amount of Lactobacillus spp. Our results also showed a trend in the incidence of elevated Desulfovibrio spp. in children with autism reaffirmed by a very strong association of the amou…

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The microgenderome revealed: sex differences in bidirectional interactions between the microbiota, hormones, immunity and disease susceptibility.

Sex differences in immunity are well described in the literature and thought to be mainly driven by sex hormones and sex-linked immune response genes. The gastrointestinal tract (GIT) is one of the largest immune organs in the body and contains multiple immune cells in the GIT-associated lymphoid tissue, Peyer's patches and elsewhere, which together have profound effects on local and systemic inflammation. The GIT is colonised with microbial communities composed of bacteria, fungi and viruses, collectively known as the GIT microbiota. The GIT microbiota drives multiple interactions locally with immune cells that regulate the homeostatic environment and systemically in diverse tissues. It is becoming evident that the microbiota differs between the sexes, both in animal models and in humans, and these sex differences often lead to sex-dependent changes in local GIT inflammation, systemic i…

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The Gut Microbiota and Alzheimer's Disease.

The gut microbiota comprises a complex community of microorganism species that resides in our gastrointestinal ecosystem and whose alterations influence not only various gut disorders but also central nervous system disorders such as Alzheimer's disease (AD). AD, the most common form of dementia, is a neurodegenerative disorder associated with impaired cognition and cerebral accumulation of amyloid-β peptides (Aβ). Most notably, the microbiota-gut-brain axis is a bidirectional communication system that is not fully understood, but includes neural, immune, endocrine, and metabolic pathways. Studies in germ-free animals and in animals exposed to pathogenic microbial infections, antibiotics, probiotics, or fecal microbiota transplantation suggest a role for the gut microbiota in host cognition or AD-related pathogenesis. The increased permeability of the gut and blood-brain barrier induced …

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Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis.

Background: Conditions of excess androgen in women, such as polycystic ovary syndrome (PCOS), often exhibit intergenerational transmission. One way in which the risk for PCOS may be increased in daughters of affected women is through exposure to elevated androgens in utero. Hyperandrogenemic conditions have serious health consequences, including increased risk for hypertension and cardiovascular disease. Recently, gut dysbiosis has been found to induce hypertension in rats, such that blood pressure can be normalized through fecal microbial transplant. Therefore, we hypothesized that the hypertension seen in PCOS has early origins in gut dysbiosis caused by in utero exposure to excess androgen. We investigated this hypothesis with a model of prenatal androgen (PNA) exposure and maternal hyperandrogenemia by single-injection of testosterone cypionate or sesame oil vehicle (VEH) to pregnant…

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Effects of Fecal Microbiome Transfer in Adolescents With Obesity: The Gut Bugs Randomized Controlled Trial.

Importance: Treatment of pediatric obesity is challenging. Preclinical studies in mice indicated that weight and metabolism can be altered by gut microbiome manipulation. Objective: To assess efficacy of fecal microbiome transfer (FMT) to treat adolescent obesity and improve metabolism. Design, setting, and participants: This randomized, double-masked, placebo-controlled trial (October 2017-March 2019) with a 26-week follow-up was conducted among adolescents aged 14 to 18 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or more in Auckland, New Zealand. A total of 87 individuals took part-565 individuals responded to advertisements, 328 were ineligible, and 150 declined participation. Clinical data were analyzed from September 2019 to May 2020. Interventions: Single course of oral encapsulated fecal microbiome from 4 healthy …

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High-fiber diet mitigates maternal obesity-induced cognitive and social dysfunction in the offspring via gut-brain axis.

Maternal obesity has been reported to be related to neurodevelopmental disorders in the offspring. However, the underlying mechanisms and effective interventions remain unclear. This cross-sectional study with 778 children aged 7-14 years in China indicated that maternal obesity is strongly associated with children's lower cognition and sociality. Moreover, it has been demonstrated that maternal obesity in mice disrupted the behavior and gut microbiome in offspring, both of which were restored by a high-fiber diet in either dams or offspring via alleviating synaptic impairments and microglial maturation defects. Co-housing and feces microbiota transplantation experiments revealed a causal relationship between microbiota and behavioral changes. Moreover, treatment with the microbiota-derived short-chain fatty acids also alleviated the behavioral deficits in the offspring of obese dams. To…

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Dietary Influences on Gut Microbiota and Their Role in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major contributor to liver-related morbidity, cardiovascular disease, and metabolic complications. Lifestyle interventions, including diet and exercise, are first line in treating MASLD. Dietary approaches such as the low-glycemic-index Mediterranean diet, the ketogenic diet, intermittent fasting, and high fiber diets have demonstrated potential in addressing the metabolic dysfunction underlying this condition. The development and progression of MASLD are closely associated with taxonomic shifts in gut microbial communities, a relationship well-documented in the literature. Given the importance of diet as a primary treatment for MASLD, it is important to understand how gut microbiota and their metabolic byproducts mediate favorable outcomes induced by healthy dietary patterns. Conversely, microbiota changes conferred b…

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Dietary Implications of the Bidirectional Relationship between the Gut Microflora and Inflammatory Diseases with Special Emphasis on Irritable Bowel Disease: Current and Future Perspective.

The immune system is vital for safeguarding the human body against infections and inflammatory diseases. The role of diet and meal patterns in modulating immune function is complex, and highlighting this topic is crucial for identifying potential ways to improve immune health. In Europe, the Mediterranean diet and Western diet are the most common dietary patterns, and gaining an understanding of how they affect immune function is essential for public health. There are numerous inflammatory diseases that are observed in younger and older people. Some of the common diseases include polymyalgia rheumatica (PMR), spinal muscular atrophy (SMA), vasculitis, sarcopenia, cirrhosis, cancer, and fibromyalgia, but the main focus in this review article is on irritable bowel disease (IBD). In general, dietary choices can have an immense impact on the microbial flora of the gut in people with inflamma…

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Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders.

Emerging evidence indicates that gut microbiota is important in the regulation of brain activity and cognitive functions. Microbes mediate communication among the metabolic, peripheral immune, and central nervous systems via the microbiota-gut-brain axis. However, it is not well understood how the gut microbiome and neurons in the brain mutually interact or how these interactions affect normal brain functioning and cognition. We summarize the mechanisms whereby the gut microbiota regulate the production, transportation, and functioning of neurotransmitters. We also discuss how microbiome dysbiosis affects cognitive function, especially in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.

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Gut microbiota-brain axis in depression: The role of neuroinflammation.

Major depressive disorder (MDD) is a psychiatric condition that affects a large number of people in the world, and the treatment existents do not work for all individuals affected. Thus, it is believed that other systems or pathways which regulate brain networks involved in mood regulation and cognition are associated with MDD pathogenesis. Studies in humans and animal models have been shown that in MDD there are increased levels of inflammatory mediators, including cytokines and chemokines in both periphery and central nervous system (CNS). In addition, microglial activation appears to be a key event that triggers changes in signaling cascades and gene expression that would be determinant for the onset of depressive symptoms. Recent researches also point out that changes in the gut microbiota would lead to a systemic inflammation that in different ways would reach the CNS modulating inf…

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Current Perspectives on Gut Microbiome Dysbiosis and Depression.

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, particularl…

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Gut Microbiome: Profound Implications for Diet and Disease.

The gut microbiome plays an important role in human health and influences the development of chronic diseases ranging from metabolic disease to gastrointestinal disorders and colorectal cancer. Of increasing prevalence in Western societies, these conditions carry a high burden of care. Dietary patterns and environmental factors have a profound effect on shaping gut microbiota in real time. Diverse populations of intestinal bacteria mediate their beneficial effects through the fermentation of dietary fiber to produce short-chain fatty acids, endogenous signals with important roles in lipid homeostasis and reducing inflammation. Recent progress shows that an individual's starting microbial profile is a key determinant in predicting their response to intervention with live probiotics. The gut microbiota is complex and challenging to characterize. Enterotypes have been proposed using metrics…

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Feeding melancholic microbes: MyNewGut recommendations on diet and mood.

Depression is a highly prevalent disorder which exerts a major economic impact in all European countries. The brain-gut-microbiota axis has been described as a new paradigm for advancing understanding and treatment of the disorder. There is now over-whelming evidence to support the fact that gut microbes have a major impact on central neurochemistry and behaviour, especially stress related disorders such as depression. Recent studies indicate that patients with depression have a gut dysbiosis. The reason for this dysbiosis is uncertain. Over recent decades, dietary patterns in Europe and elsewhere have undergone major compositional changes, with increased intakes of red meat, high fat foods, and refined sugars. Individuals who consume a Mediterranean diet have lower rates of depression and a recent study suggests that a Mediterranean diet may have antidepressant properties. Assuming this…

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