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

From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways.

The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the …

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Chinese medicine formula Kai-Xin-San ameliorates depression-like behaviours in chronic unpredictable mild stressed mice by regulating gut microbiota-inflammation-stress system.

Ethnopharmacological relevance: Kai-Xin-San (KXS) has been prescribed by TCM doctors for treating psychiatric diseases with the core symptoms of anhedonia, amnesia, and dizziness. According to the symptoms of patients, KXS series formulae are created by varying the compatible ratio of herbs. Today, these formulae are still used in the clinic to treat major depressive disorders. Aim of the study: We hoped to evaluate the antidepressant-like effect of Kai-Xin-San via regulation of the gut-brain axis. Materials and methods: Standardized extracts of three representative compatible ratios of KXS had been prepared, and quality control of the extracts was performed by HPLC-MS/MS. Chronic unpredictable mild stress (CUMS)-induced depression-like mice were used as the depression animal model. After KXS treatment, the antidepressant-like effects of KXS were assessed by behavioural tests. The gut mi…

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Bifidobacterium with the role of 5-hydroxytryptophan synthesis regulation alleviates the symptom of depression and related microbiota dysbiosis.

Depression disorder is rapidly advancing worldwide, and therapeutic strategy through gut-brain axis has been proven to be effective in the treatment. Here we studied the effect of lactic acid bacteria (LAB) treatment on depression. C57BL/6J mice were administered with LAB during a 5-week chronic unpredictable mild stress. Bifidobacterium longum subsp. infantis E41 and Bifidobacterium breve M2CF22M7, which improved the expression of Tph1 and secretion of 5-hydroxytryptophan (5-HTP) in RIN14B cells, significantly reduced depressive behaviors of mice in the forced swim test, sucrose preference test and step-down test, as well as increased the level of 5-hydroxytryptamine and brain-derived neurotrophic factor concentration in brain. Besides, M2CF22M7 reduced the serum corticosterone level. E41 increased cecal butyrate level, which significantly and positively correlated with some depression-…

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Gut microbiota and its metabolites in depression: from pathogenesis to treatment.

Major depressive disorder is one of the most disabling mental disorders worldwide. Increasing preclinical and clinical studies have highlighted that compositional and functional (e.g., metabolite) changes in gut microbiota, known as dysbiosis, are associated with the onset and progression of depression via regulating the gut-brain axis. However, the gut microbiota and their metabolites present a double-edged sword in depression. Dysbiosis is involved in the pathogenesis of depression while, at the same time, offering a novel therapeutic target. In this review, we describe the association between dysbiosis and depression, drug-microbiota interactions in antidepressant treatment, and the potential health benefits of microbial-targeted therapeutics in depression, including dietary interventions, fecal microbiota transplantation, probiotics, prebiotics, synbiotics, and postbiotics. With the …

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Gut-brain Axis and migraine headache: a comprehensive review.

The terminology "gut-brain axis "points out a bidirectional relationship between the GI system and the central nervous system (CNS). To date, several researches have shown that migraine is associated with some gastrointestinal (GI) disorders such as Helicobacter pylori (HP) infection, irritable bowel syndrome (IBS), and celiac disease (CD). The present review article aims to discuss the direct and indirect evidence suggesting relationships between migraine and the gut-brain axis. However, the mechanisms explaining how the gut and the brain may interact in patients with migraine are not entirely clear. Studies suggest that this interaction seems to be influenced by multiple factors such as inflammatory mediators (IL-1β, IL-6, IL-8, and TNF-α), gut microbiota profile, neuropeptides and serotonin pathway, stress hormones and nutritional substances. Neuropeptides including CGRP, SP, VIP, NPY…

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Alcohol, liver disease and the gut microbiota.

Alcoholic liver disease, which ranges from mild disease to alcoholic hepatitis and cirrhosis, is a leading cause of morbidity and mortality worldwide. Alcohol intake can lead to changes in gut microbiota composition, even before liver disease development. These alterations worsen with advancing disease and could be complicit in disease progression. Microbial function, especially related to bile acid metabolism, can modulate alcohol-associated injury even in the presence of cirrhosis and alcoholic hepatitis. Microbiota changes might also alter brain function, and the gut-brain axis might be a potential target to reduce alcoholic relapse risk. Gut microbiota manipulation including probiotics, faecal microbial transplant and antibiotics has been studied in alcoholic liver disease with varying success. Further investigation of the modulation of the gut-liver axis is relevant, as most of thes…

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Probiotics, gut microbiota, and their influence on host health and disease.

The gastrointestinal tract of mammals hosts a high and diverse number of different microorganisms, known as intestinal microbiota. Many probiotics were originally isolated from the gastrointestinal tract, and they were defined by the Food and Agriculture Organization of the United Nations (FAO)/WHO as "live microorganisms which when administered in adequate amounts confer a health benefit on the host." Probiotics exert their beneficial effects on the host through four main mechanisms: interference with potential pathogens, improvement of barrier function, immunomodulation and production of neurotransmitters, and their host targets vary from the resident microbiota to cellular components of the gut-brain axis. However, in spite of the wide array of beneficial mechanisms deployed by probiotic bacteria, relatively few effects have been supported by clinical data. In this regard, different p…

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Microbiome, probiotics and neurodegenerative diseases: deciphering the gut brain axis.

The gut microbiota is essential to health and has recently become a target for live bacterial cell biotherapies for various chronic diseases including metabolic syndrome, diabetes, obesity and neurodegenerative disease. Probiotic biotherapies are known to create a healthy gut environment by balancing bacterial populations and promoting their favorable metabolic action. The microbiota and its respective metabolites communicate to the host through a series of biochemical and functional links thereby affecting host homeostasis and health. In particular, the gastrointestinal tract communicates with the central nervous system through the gut-brain axis to support neuronal development and maintenance while gut dysbiosis manifests in neurological disease. There are three basic mechanisms that mediate the communication between the gut and the brain: direct neuronal communication, endocrine signa…

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Prebiotic effect on mood in obese patients is determined by the initial gut microbiota composition: A randomized, controlled trial.

Background and aims: Metabolic and behavioural diseases, which are often related to obesity, have been associated to alterations of the gut microbiota considered as an interesting therapeutic target. We have analyzed in a cohort of obese patients treated with prebiotic inulin versus placebo the potential link between gut microbiota changes occurring upon intervention and their effect on psychological parameters (mood and cognition). Methods: A randomized, single-blinded, multicentric, placebo-controlled trial was conducted in 106 obese patients assigned to two groups: prebiotic versus placebo, who received respectively 16 g/d of native inulin or maltodextrin combined with dietary advice to consume inulin-rich or -poor vegetables for 3 months as well as to restrict caloric intake. Anthropometric measurements, food intake, psychological questionnaires, serum measures, and fecal microbiome …

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Colon-delivered short-chain fatty acids attenuate the cortisol response to psychosocial stress in healthy men: a randomized, placebo-controlled trial.

Short-chain fatty acids (SCFAs) are products of microbial fermentation of dietary fiber in the colon and may mediate microbiota-gut-brain communication. However, their role in modulating psychobiological processes that underlie the development of stress- and anxiety-related disorders is not mechanistically studied in humans. In this triple-blind, randomized, placebo-controlled intervention trial, we examine in a parallel group design the effects of 1-week colonic SCFA-mixture delivery in doses equivalent to fermentation of 10 g or 20 g of arabinoxylan oligosaccharides on responses to psychosocial stress and fear tasks in 66 healthy men. We demonstrate that low and high doses of SCFAs significantly attenuate the cortisol response to psychosocial stress compared to placebo. Both doses of SCFAs increase serum SCFA levels and this increase in circulating SCFAs co-varies significantly with th…

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The Role of the Microbiome-Brain-Gut Axis in the Pathogenesis of Depressive Disorder.

The role of gut microbiota and its association with the central nervous system via the microbiome-brain-gut axis has been widely discussed in the literature. The aim of this review is to investigate the impact of gut microbiota on the development of depression and underlying molecular mechanisms. There are two possible pathways in which this interaction might occur. The first one suggests that depressive disorder could lead to dysbiosis and one of the causes may be the influence on the hypothalamic-pituitary-adrenal (HPA) axis. The second one considers if changes in the composition of gut microbiota might cause depressive disorder. The mechanisms that could be responsible for this interaction include the secretion of neurotransmitters, gut peptides and the activation of the immune system. However, current knowledge on this topic does not allow for us to state an unambiguous conclusion, a…

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The Gut-Brain Axis in Schizophrenia: The Implications of the Gut Microbiome and SCFA Production.

Schizophrenia, a severe mental illness affecting about 1% of the population, manifests during young adulthood, leading to abnormal mental function and behavior. Its multifactorial etiology involves genetic factors, experiences of adversity, infection, and gene-environment interactions. Emerging research indicates that maternal infection or stress during pregnancy may also increase schizophrenia risk in offspring. Recent research on the gut-brain axis highlights the gut microbiome's potential influence on central nervous system (CNS) function and mental health, including schizophrenia. The gut microbiota, located in the digestive system, has a significant role to play in human physiology, affecting immune system development, vitamin synthesis, and protection against pathogenic bacteria. Disruptions to the gut microbiota, caused by diet, medication use, environmental pollutants, and stress…

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Clinical, gut microbial and neural effects of a probiotic add-on therapy in depressed patients: a randomized controlled trial.

A promising new treatment approach for major depressive disorder (MDD) targets the microbiota-gut-brain (MGB) axis, which is linked to physiological and behavioral functions affected in MDD. This is the first randomized controlled trial to determine whether short-term, high-dose probiotic supplementation reduces depressive symptoms along with gut microbial and neural changes in depressed patients. Patients with current depressive episodes took either a multi-strain probiotic supplement or placebo over 31 days additionally to treatment-as-usual. Assessments took place before, immediately after and again four weeks after the intervention. The Hamilton Depression Rating Sale (HAM-D) was assessed as primary outcome. Quantitative microbiome profiling and neuroimaging was used to detect changes along the MGB axis. In the sample that completed the intervention (probiotics N = 21, placebo N = 26…

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Intermittent Fasting Improves Cardiometabolic Risk Factors and Alters Gut Microbiota in Metabolic Syndrome Patients.

Context: Intermittent fasting (IF) is an effective strategy to improve cardiometabolic health. Objective: The objective of this work is to examine the effects of IF on cardiometabolic risk factors and the gut microbiota in patients with metabolic syndrome (MS). Design and setting: A randomized clinical trial was conducted at a community health service center. Patients: Participants included adults with MS, age 30 to 50 years. Intervention: Intervention consisted of 8 weeks of "2-day" modified IF. Main outcome measure: Cardiometabolic risk factors including body composition, oxidative stress, inflammatory cytokines, and endothelial function were assessed at baseline and at 8 weeks. The diversity, composition, and functional pathways of the gut microbiota, as well as circulating gut-derived metabolites, were measured. Results: Thirty-nine patients with MS were included: 21 in the IF group …

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PROVIT: Supplementary Probiotic Treatment and Vitamin B7 in Depression-A Randomized Controlled Trial.

Gut microbiota are suspected to affect brain functions and behavior as well as lowering inflammation status. Therefore, an effect on depression has already been suggested by recent research. The aim of this randomized double-blind controlled trial was to evaluate the effect of probiotic treatment in depressed individuals. Within inpatient care, 82 currently depressed individuals were randomly assigned to either receive a multistrain probiotic plus biotin treatment or biotin plus placebo for 28 days. Clinical symptoms as well as gut microbiome were analyzed at the begin of the study, after one and after four weeks. After 16S rRNA analysis, microbiome samples were bioinformatically explored using QIIME, SPSS, R and Piphillin. Both groups improved significantly regarding psychiatric symptoms. Ruminococcus gauvreauii and Coprococcus 3 were more abundant and β-diversity was higher in the prob…

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A meta-analysis of the use of probiotics to alleviate depressive symptoms.

Introduction: Some preclinical and clinical studies have demonstrated the positive impact of probiotic supplementation on depressive symptoms. This paper aims to provide an updated meta-analysis on the topic. Methods: Using the keywords [probiotics OR gut OR microflora OR microbiome OR bacteria OR yeast OR yoghurt OR lactobacillus OR bifidobacterium] AND [mood OR depression OR MDD OR suicide], a preliminary search on the PubMed, Ovid, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR) and Cochrane Field for Complementary Medicine database yielded 917 papers published in English between 1-Jan-1960 and 1-June-2017. Results: 10 clinical trials with a total of 1349 patients were reviewed, comparing the use of probiotics to placebo controls. There was no significant difference in mood between the treatment and placebo group post-interventio…

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Intestinal microbiota in health and disease: role of bifidobacteria in gut homeostasis.

The pool of microbes inhabiting our body is known as "microbiota" and their collective genomes as "microbiome". The colon is the most densely populated organ in the human body, although other parts, such as the skin, vaginal mucosa, or respiratory tract, also harbour specific microbiota. This microbial community regulates some important metabolic and physiological functions of the host, and drives the maturation of the immune system in early life, contributing to its homeostasis during life. Alterations of the intestinal microbiota can occur by changes in composition (dysbiosis), function, or microbiota-host interactions and they can be directly correlated with several diseases. The only disease in which a clear causal role of a dysbiotic microbiota has been demonstrated is the case of Clostridium difficile infections. Nonetheless, alterations in composition and function of the microbiot…

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Inflammatory Depression-Mechanisms and Non-Pharmacological Interventions.

Treatment of depression is hampered by the failure to identify distinct symptom profiles with distinct pathophysiologies that differentially respond to distinct treatments. We posit that inflammatory depression is a meaningful depression subtype associated with specific symptoms and biological abnormalities. We review several upstream, potentially causative, mechanisms driving low-grade inflammation in this subtype of depression. We also discuss downstream mechanisms mediating the link between inflammation and symptoms of depression, including alterations in dopaminergic neurotransmission and tryptophan metabolism. Finally, we review evidence for several non-pharmacological interventions for inflammatory depression, including probiotics, omega-3 fatty acids, and physical exercise interventions. While some evidence suggests that these interventions may be efficacious in inflammatory depre…

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Establishment of the intestinal microbiota and its role for atopic dermatitis in early childhood.

Background: Perturbations in the intestinal microbiota may disrupt mechanisms involved in the development of immunologic tolerance. The present study aimed to examine the establishment of the infant microbiota and its association to the development of atopic dermatitis (AD). Methods: Within a randomized, placebo-controlled trial on the prevention of AD by oral supplementation of a bacterial lysate between week 5 and the end of month 7, feces was collected at the ages of 5 weeks (n = 571), 13 weeks (n = 332), and 31 weeks (n = 499) and subjected to quantitative PCRs to detect bifidobacteria, bacteroides, lactobacilli, Escherichia coli, Clostridium difficile, and Clostridium cluster I. Results: Birth mode, breast-feeding but also birth order had a strong effect on the microbiota composition. With increasing number of older siblings the colonization rates at age 5 weeks of lactobacilli (P <…

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Diabesity and mood disorders: Multiple links through the microbiota-gut-brain axis.

The global prevalence of diabesity is on the rise, and the clinical, social and economic health burden arising from this epidemic is aggravated by a significant co-morbidity of diabesity with neuropsychiatric disease, particularly depression. Importantly, not only is the prevalence of mood disorders elevated in patients with type 2 diabetes, depressed patients are also more prone to develop diabetes. This reciprocal relationship calls for a molecular and systemic analysis of diabesity-brain interactions to guide preventive and therapeutic strategies. The analysis we are presenting in this review is modelled on the microbiota-gut-brain axis, which provides the brain with information from the gut not only via the nervous system, but also via a continuous stream of microbial, endocrine, metabolic and immune messages. This communication network offers important clues as to how obesity and di…

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The link between inflammation, bugs, the intestine and the brain in alcohol dependence.

In recent years, some new processes have been proposed to explain how alcohol may influence behavior, psychological symptoms and alcohol seeking in alcohol-dependent subjects. In addition to its important effect on brain and neurotransmitters equilibrium, alcohol abuse also affects peripheral organs including the gut. By yet incompletely understood mechanisms, chronic alcohol abuse increases intestinal permeability and alters the composition of the gut microbiota, allowing bacterial components from the gut lumen to reach the systemic circulation. These gut-derived bacterial products are recognized by immune cells circulating in the blood or residing in target organs, which consequently synthesize and release pro-inflammatory cytokines. Circulating cytokines are considered important mediators of the gut-brain communication, as they can reach the central nervous system and induce neuroinfl…

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Bifidobacterium breve CCFM1025 attenuates major depression disorder via regulating gut microbiome and tryptophan metabolism: A randomized clinical trial.

Objective: Psychobiotics, as a novel class of probiotics mainly acting on the gut-brain axis, have shown promising prospects in treating psychiatric disorders. Bifidobacterium breve CCFM1025 was validated to have an antidepressant-like effect in mice. This study aims to assess its psychotropic potential in managing major depression disorder (MDD) and unravel the underlying mechanisms. Methods: Clinical Trial Registration: https://www.chictr.org.cn/index.aspx (identifier: NO. ChiCTR2100046321). Patients (n = 45) diagnosed with MDD were randomly assigned to the Placebo (n = 25) and CCFM1025 (n = 20) groups. The freeze-dried CCFM1025 in a dose of viable bacteria of 1010 CFU was given to MDD patients daily for four weeks, while the placebo group was given maltodextrin. Changes from baseline in psychometric and gastrointestinal symptoms were evaluated using Hamilton Depression Rating scale-24…

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Interplay of gut microbiota and oxidative stress: Perspective on neurodegeneration and neuroprotection.

Background: Recent research on the implications of gut microbiota on brain functions has helped to gather important information on the relationship between them. Pathogenesis of neurological disorders is found to be associated with dysregulation of gut-brain axis. Some gut bacteria metabolites are found to be directly associated with the increase in reactive oxygen species levels, one of the most important risk factors of neurodegeneration. Besides their morbid association, gut bacteria metabolites are also found to play a significant role in reducing the onset of these life-threatening brain disorders. Aim of review: Studies done in the recent past raises two most important link between gut microbiota and the brain: "gut microbiota-oxidative stress-neurodegeneration" and gut microbiota-antioxidant-neuroprotection. This review aims to gives a deep insight to our readers, of the collectiv…

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Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer's disease.

Gut microbiota represents a diverse and dynamic population of microorganisms harboring the gastrointestinal tract, which influences the host health and disease. Gut microbiota communicates with the brain and vice versa through complex bidirectional communication systems - the gut-brain axis, which integrates the peripheral intestinal function with emotional and cognitive brain centers via neuro-immuno-endocrine mediators. Aging alters the gut microbial population, which not only leads to gastrointestinal disturbances but also causes central nervous system (CNS) disorders such as dementia. Alzheimer's disease (AD) is the most common form of dementia affecting the older person, characterized by beta-amyloid (Aβ) plaques and neurofibrillary tangles leading to the cognitive deficit and memory impairment. Multiple experimental and clinical studies revealed the role of gut microbiota in host c…

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Role of the Intestinal Microbiome, Intestinal Barrier and Psychobiotics in Depression.

The intestinal microbiota plays an important role in the pathophysiology of depression. As determined, the microbiota influences the shaping and modulation of the functioning of the gut-brain axis. The intestinal microbiota has a significant impact on processes related to neurotransmitter synthesis, the myelination of neurons in the prefrontal cortex, and is also involved in the development of the amygdala and hippocampus. Intestinal bacteria are also a source of vitamins, the deficiency of which is believed to be related to the response to antidepressant therapy and may lead to exacerbation of depressive symptoms. Additionally, it is known that, in periods of excessive activation of stress reactions, the immune system also plays an important role, negatively affecting the tightness of the intestinal barrier and intestinal microflora. In this review, we have summarized the role of the gu…

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