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

Roles of Birth Mode and Infant Gut Microbiota in Intergenerational Transmission of Overweight and Obesity From Mother to Offspring.

Importance: Maternal overweight, which often results in cesarean delivery, is a strong risk factor for child overweight. Little is known about the joint contribution of birth mode and microbiota in the infant gut to the association between maternal prepregnancy overweight and child overweight. Objective: To investigate the association of birth mode with microbiota in the infant gut, and whether this mediates the association between maternal and child overweight. Design, setting, and participants: An observational study was conducted of 935 full-term infants born between January 1, 2009, and December 31, 2012, in the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Maternal prepregnancy body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared using height and weight data taken from medical records or maternal report. Infant gut …

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Microbiota in anorexia nervosa: The triangle between bacterial species, metabolites and psychological tests.

Anorexia nervosa (AN) is a psychiatric disease with devastating physical consequences, with a pathophysiological mechanism still to be elucidated. Metagenomic studies on anorexia nervosa have revealed profound gut microbiome perturbations as a possible environmental factor involved in the disease. In this study we performed a comprehensive analysis integrating data on gut microbiota with clinical, anthropometric and psychological traits to gain new insight in the pathophysiology of AN. Fifteen AN women were compared with fifteen age-, sex- and ethnicity-matched healthy controls. AN diet was characterized by a significant lower energy intake, but macronutrient analysis highlighted a restriction only in fats and carbohydrates consumption. Next generation sequencing showed that AN intestinal microbiota was significantly affected at every taxonomic level, showing a significant increase of En…

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Microbiota-related Changes in Bile Acid & Tryptophan Metabolism are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism.

Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental conditions worldwide. There is growing awareness that ASD is highly comorbid with gastrointestinal distress and altered intestinal microbiome, and that host-microbiome interactions may contribute to the disease symptoms. However, the paucity of knowledge on gut-brain axis signaling in autism constitutes an obstacle to the development of precision microbiota-based therapeutics in ASD. To this end, we explored the interactions between intestinal microbiota, gut physiology and social behavior in a BTBR T+Itpr3tf/J mouse model of ASD. Here we show that a reduction in the relative abundance of very particular bacterial taxa in the BTBR gut - namely, bile-metabolizing Bifidobacterium and Blautia species, - is associated with deficient bile acid and tryptophan metabolism in the intestine, marked gastrointestinal dysf…

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Metabolomic signature of exposure and response to citalopram/escitalopram in depressed outpatients.

Metabolomics provides valuable tools for the study of drug effects, unraveling the mechanism of action and variation in response due to treatment. In this study we used electrochemistry-based targeted metabolomics to gain insights into the mechanisms of action of escitalopram/citalopram focusing on a set of 31 metabolites from neurotransmitter-related pathways. Overall, 290 unipolar patients with major depressive disorder were profiled at baseline, after 4 and 8 weeks of drug treatment. The 17-item Hamilton Depression Rating Scale (HRSD17) scores gauged depressive symptom severity. More significant metabolic changes were found after 8 weeks than 4 weeks post baseline. Within the tryptophan pathway, we noted significant reductions in serotonin (5HT) and increases in indoles that are known to be influenced by human gut microbial cometabolism. 5HT, 5-hydroxyindoleacetate (5HIAA), and the ra…

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Nutrition Strategy and Life Style in Polycystic Ovary Syndrome-Narrative Review.

Here we present an extensive narrative review of the broadly understood modifications to the lifestyles of women with polycystic ovary syndrome (PCOS). The PubMed database was analyzed, combining PCOS entries with causes, diseases, diet supplementation, lifestyle, physical activity, and use of herbs. The metabolic pathways leading to disturbances in lipid, carbohydrate, and hormonal metabolism in targeted patients are described. The article refers to sleep disorders, changes in mental health parameters, and causes of oxidative stress and inflammation. These conditions consistently lead to the occurrence of severe diseases in patients suffering from diabetes, the fatty degeneration of internal organs, infertility, atherosclerosis, cardiovascular diseases, dysbiosis, and cancer. The modification of lifestyles, diet patterns and proper selection of nutrients, pharmacological and natural sup…

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Interoception, Trait Anxiety, and the Gut Microbiome: A Cognitive and Physiological Model.

Trait anxiety is characterized as a constant and often subliminal state that persists during daily life. Interoception is the perception of internal states and sensations, including from the autonomic nervous system. This review aims to develop a predictive model to explain the emergence, manifestations, and maintenance of trait anxiety. The model begins with the assumption that anxiety states arise from active interoceptive inference. The subsequent activation of autonomic responses results from aversive sensory encounters. A cognitive model is proposed for trait anxiety that includes the aversive sensory components from interoception, exteroception, and proprioception. A further component of the hypothesis is that repeated exposure to subliminal anxiety-evoking sensory elements can lead to an overgeneralization of this response to other inputs that are generally non-aversive. Increased…

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Diet and gut microbiome interactions in gynecologic cancer.

Over the last decade, there has been a dramatic surge in research exploring the human gut microbiome and its role in health and disease. It is now widely accepted that commensal microorganisms coexist within the human gastrointestinal tract and other organs, including those of the reproductive tract. These microorganisms, which are collectively known as the "microbiome", contribute to maintaining host physiology and to the development of pathology. Next generation sequencing and multi-'omics' technology has enriched our understanding of the complex and interdependent relationship that exists between the host and microbiome. Global changes in the microbiome are known to be influenced by dietary, genetic, lifestyle, and environmental factors. Accumulating data have shown that alterations in the gut microbiome contribute to the development, prognosis and treatment of many disease states inc…

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Nutritional Interventions for Treating Cancer-Related Fatigue: A Qualitative Review.

Cancer-related fatigue (CRF) is a debilitating syndrome that persists for many cancer survivors for years after treatment. Symptoms include early and persistent fatigue, functional decline, depression, and cognitive difficulties. Inflammation, assessed using pro-inflammatory biomarkers, is increased in cancer survivors with fatigue and treatments for fatigue are often aimed at reducing inflammation. Additionally, cancer and its treatment lead to nutritional complications, changes in body composition, and nutritional deficiencies that potentially weaken the cancer survivor and impact CRF. We conducted a qualitative review of clinical trials that assessed nutritional interventions for preventing and treating CRF. Further studies were examined that used nutritional interventions to address inflammation and fatigue, due to the dearth of nutrition research directly related to CRF. Dietary int…

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Mechanisms by which Stress Affects the Experimental and Clinical Inflammatory Bowel Disease (IBD): Role of Brain-Gut Axis.

Background: Stress of different origin is known to alter so called "braingut axis" and contributes to a broad array of gastrointestinal disorders including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and other functional gastrointestinal diseases. The stressful situations and various stressors including psychosocial events, heat, hypo- and hyperthermia may worsen the course of IBD via unknown mechanism. The aims of this paper were to provide an overview of experimental and clinical evidences that stress activates the brain-gut axis which results in a mucosal mast cells activation and an increase in the production of proinflammatory cytokines and other endocrine and humoral mediators. Methods: Research and online content related to effects of stress on lower bowel disorders are reviewed and most important mechanisms are delineated. Results: Brain conveys the neural, e…

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Characterization of the nasal and oral microbiota of detection dogs.

Little is known about physiological factors that affect the sense of olfaction in dogs. The objectives of this study were to describe the canine nasal and oral microbiota in detection dogs. We sought to determine the bacterial composition of the nasal and oral microbiota of a diverse population of detection canines. Nasal and oral swabs were collected from healthy dogs (n = 81) from four locations-Alabama, Georgia, California, and Texas. Nasal and oral swabs were also collected from a second cohort of detection canines belonging to three different detection job categories: explosive detection dogs (SP-E; n = 22), patrol and narcotics detection dogs (P-NDD; n = 15), and vapor wake dogs (VWD-E; n = 9). To understand if the nasal and oral microbiota of detection canines were variable, sample collection was repeated after 7 weeks in a subset of dogs. DNA was extracted from the swabs and used…

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Similar Fecal Microbiota Signatures in Patients With Diarrhea-Predominant Irritable Bowel Syndrome and Patients With Depression.

Background & aims: Patients with irritable bowel syndrome (IBS) often have psychiatric comorbidities. Alterations in the intestinal microbiota have been associated with IBS and depression, but it is not clear if there is a microbial relationship between these disorders. We studied the profiles of fecal microbiota samples from patients with IBS, depression, or comorbidities of IBS and depression; we determined the relationships among these profiles and clinical and pathophysiological features of these disorders. Methods: We used 454 pyrosequencing to analyze fecal microbiota samples from 100 subjects (40 with diarrhea-predominant IBS [IBS-D], 15 with depression, 25 with comorbidities of IBS and depression, and 20 healthy individuals [controls]), recruited at Peking University. Abdominal and psychological symptoms were evaluated with validated questionnaires. Visceral sensitivity was evalu…

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The Impact of Systemic Inflammation on Alzheimer's Disease Pathology.

Alzheimer's disease (AD) is a devastating age-related neurodegenerative disorder with an alarming increasing prevalence. Except for the recently FDA-approved Aducanumab of which the therapeutic effect is not yet conclusively proven, only symptomatic medication that is effective for some AD patients is available. In order to be able to design more rational and effective treatments, our understanding of the mechanisms behind the pathogenesis and progression of AD urgently needs to be improved. Over the last years, it became increasingly clear that peripheral inflammation is one of the detrimental factors that can contribute to the disease. Here, we discuss the current understanding of how systemic and intestinal (referred to as the gut-brain axis) inflammatory processes may affect brain pathology, with a specific focus on AD. Moreover, we give a comprehensive overview of the different prec…

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Gut Microbiota and Time-Restricted Feeding/Eating: A Targeted Biomarker and Approach in Precision Nutrition.

Each individual has a unique gut microbiota; therefore, the genes in our microbiome outnumber the genes in our genome by about 150 to 1. Perturbation in host nutritional status influences gut microbiome composition and vice versa. The gut microbiome can help in producing vitamins, hormones, and other active metabolites that support the immune system; harvest energy from food; aid in digestion; protect against pathogens; improve gut transit and function; send signals to the brain and other organs; oscillate the circadian rhythm; and coordinate with the host metabolism through multiple cellular pathways. Gut microbiota can be influenced by host genetics, medications, diet, and lifestyle factors from preterm to aging. Aligning with precision nutrition, identifying a personalized microbiome mandates the provision of the right nutrients at the right time to the right patient. Thus, before pre…

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Diet and the microbiota - gut - brain-axis: a primer for clinical nutrition.

Purpose of review: Diet is an essential modulator of the microbiota - gut - brain communication in health and disease. Consequently, diet-induced microbiome states can impact brain health and behaviour. The integration of microbiome into clinical nutrition perspectives of brain health is sparse. This review will thus focus on emerging evidence of microbiome-targeted dietary approaches with the potential to improve brain disorders. Recent findings: Research in this field is evolving toward randomized controlled trials using dietary interventions with the potential to modulate pathways of the microbiota - gut - brain-axis. Although most studies included small cohorts, the beneficial effects of Mediterranean-like diets on symptoms of depression or fermented foods on the immune function of healthy individuals shed light on how this research line can grow. With a clinical nutrition lens, we h…

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Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer's disease.

Background: The implication of gut microbiota in the control of brain functions in health and disease is a novel, currently emerging concept. Accumulating data suggest that the gut microbiota exert its action at least in part by modulating neuroinflammation. Given the link between neuroinflammatory changes and neuronal activity, it is plausible that gut microbiota may affect neuronal functions indirectly by impacting microglia, a key player in neuroinflammation. Indeed, increasing evidence suggests that interplay between microglia and synaptic dysfunction may involve microbiota, among other factors. In addition to these indirect microglia-dependent actions of microbiota on neuronal activity, it has been recently recognized that microbiota could also affect neuronal activity directly by stimulation of the vagus nerve. Main messages: The putative mechanisms of the indirect and direct impac…

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The impact of the microbiota-gut-brain axis on Alzheimer's disease pathophysiology.

The gut microbiota is a complex ecosystem that comprises of more than 100 trillion symbiotic microbial cells. The microbiota, the gut, and the brain form an association, 'the microbiota-gut-brain axis,' and synchronize the gut with the central nervous system and modify the behavior and brain immune homeostasis. The bidirectional communication between gut and brain occurs via the immune system, the vagus nerve, the enteric nervous system, and microbial metabolites, including short-chain fatty acids (SCFAs), proteins, and tryptophan metabolites. Recent studies have implicated the gut microbiota in many neurodegenerative diseases, including Alzheimer's disease (AD). In this review, we present an overview of gut microbiota, including Firmicutes, Bacteroidetes, SCFA, tryptophan, bacterial composition, besides age-related changes in gut microbiota composition, the microbiota-gut-brain axis pat…

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Cancer and the Microbiome-Influence of the Commensal Microbiota on Cancer, Immune Responses, and Immunotherapy.

The commensal microbiota has been implicated in the regulation of a diverse array of physiological processes, both within the gastrointestinal tract and at distant tissue sites. Cancer is no exception, and distinct aspects of the microbiota have been reported to have either pro- or anti-tumor effects. The functional role of the microbiota in regulating not only mucosal but also systemic immune responses has led to investigations into the impact on cancer immunotherapies, particularly with agents targeting the immunologic checkpoints PD-1 and CTLA-4. Microbial sequencing and reconstitution of germ-free mice have indicated both positive and negative regulatory bacteria likely exist, which either promote or interfere with immunotherapy efficacy. These collective findings have led to the development of clinical trials pursuing microbiome-based therapeutic interventions, with the hope of expa…

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Priming for Life: Early Life Nutrition and the Microbiota-Gut-Brain Axis.

Microbes colonize the human body during the first moments of life and coexist with the host throughout the lifespan. Intestinal microbiota and their metabolites aid in the programming of important bodily systems such as the immune and the central nervous system during critical temporal windows of development, with possible structural and functional implications throughout the lifespan. These critical developmental windows perinatally (during the first 1000 days) are susceptible timepoints for insults that can endure long lasting effects on the microbiota-gut-brain axis. Environmental and parental factors like host genetics, mental health, nutrition, delivery and feeding mode, exposure to antibiotics, immune activation and microbiota composition antenatally, are all factors that are able to modulate the microbiota composition of mother and infant and may thus regulate important bodily fun…

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Mining microbes for mental health: Determining the role of microbial metabolic pathways in human brain health and disease.

There is increasing knowledge regarding the role of the microbiome in modulating the brain and behaviour. Indeed, the actions of microbial metabolites are key for appropriate gut-brain communication in humans. Among these metabolites, short-chain fatty acids, tryptophan, and bile acid metabolites/pathways show strong preclinical evidence for involvement in various aspects of brain function and behaviour. With the identification of neuroactive gut-brain modules, new predictive tools can be applied to existing datasets. We identified 278 studies relating to the human microbiota-gut-brain axis which included sequencing data. This spanned across psychiatric and neurological disorders with a small number also focused on normal behavioural development. With a consistent bioinformatics pipeline, thirty-five of these datasets were reanalysed from publicly available raw sequencing files and the r…

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Diet and the Microbiota-Gut-Brain Axis: Sowing the Seeds of Good Mental Health.

Over the past decade, the gut microbiota has emerged as a key component in regulating brain processes and behavior. Diet is one of the major factors involved in shaping the gut microbiota composition across the lifespan. However, whether and how diet can affect the brain via its effects on the microbiota is only now beginning to receive attention. Several mechanisms for gut-to-brain communication have been identified, including microbial metabolites, immune, neuronal, and metabolic pathways, some of which could be prone to dietary modulation. Animal studies investigating the potential of nutritional interventions on the microbiota-gut-brain axis have led to advancements in our understanding of the role of diet in this bidirectional communication. In this review, we summarize the current state of the literature triangulating diet, microbiota, and host behavior/brain processes and discuss …

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Gut and vaginal microbiomes on steroids: implications for women's health.

This review discusses the interactions of steroids with the gut and vaginal microbiomes within each life phase of adult women and the implications for women's health. Each phase of a woman's life is characterized by distinct hormonal states which drive overall physiology of both host and commensal microbes. These host-microbiome interactions underlie disease pathology in disorders that affect women across their lifetime, including bacterial vaginosis, gestational diabetes, polycystic ovary syndrome (PCOS), anxiety, depression, and obesity. Although many associations between host health and microbiome composition are well defined, the mechanistic role of the microbiome in women's health outcomes is largely unknown. This review addresses potential mechanisms by which the microbiota influences women's health and highlights gaps in current knowledge.

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The Role of the Gut Microbiota in Dietary Interventions for Depression and Anxiety.

There is emerging evidence that an unhealthy dietary pattern may increase the risk of developing depression or anxiety, whereas a healthy dietary pattern may decrease it. This nascent research suggests that dietary interventions could help prevent, or be an alternative or adjunct therapy for, depression and anxiety. The relation, however, is complex, affected by many confounding variables, and is also likely to be bidirectional, with dietary choices being affected by stress and depression. This complexity is reflected in the data, with sometimes conflicting results among studies. As the research evolves, all characteristics of the relation need to be considered to ensure that we obtain a full understanding, which can potentially be translated into clinical practice. A parallel and fast-growing body of research shows that the gut microbiota is linked with the brain in a bidirectional rela…

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Tryptophan Metabolism and Related Pathways in Psychoneuroimmunology: The Impact of Nutrition and Lifestyle.

In the past, accelerated tryptophan breakdown was considered to be a feature of clinical conditions, such as infection, inflammation, and malignant disease. More recently, however, the focus has changed to include the additional modulation of tryptophan metabolism by changes in nutrition and microbiota composition. The regulation of tryptophan concentration is critical for the maintenance of systemic homeostasis because it integrates essential pathways involved in nutrient sensing, metabolic stress response, and immunity. In addition to tryptophan being important as a precursor for the synthesis of the neurotransmitter serotonin, several catabolites along the kynurenine axis are neuroactive. This emphasizes the importance of the immunometabolic fate of this amino acid for processes relevant to neuropsychiatric symptoms. In humans, besides hepatic catabolism, there is usually a strong rel…

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The contribution of the gut microbiome to neurodevelopment and neuropsychiatric disorders.

Bidirectional communication between the gut and brain is well recognized, with data now accruing for a specific role of the gut microbiota in that link, referred to as the microbiome-gut-brain axis. This review will discuss the emerging role of the gut microbiota in brain development and behavior. Animal studies have clearly demonstrated effects of the gut microbiota on gene expression and neurochemical metabolism impacting behavior and performance. Based on these changes, a modulating role of the gut microbiota has been demonstrated for a variety of neuropsychiatric disorders, including depression, anxiety, and movement including Parkinson's, and importantly for the pediatric population autism. Critical developmental windows that influence early behavioral outcomes have been identified that include both the prenatal environment and early postnatal colonization periods. The clearest data…

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Recognizing Depression from the Microbiota⁻Gut⁻Brain Axis.

Major depression is one of the leading causes of disability, morbidity, and mortality worldwide. The brain⁻gut axis functions are disturbed, revealed by a dysfunction of the brain, immune system, endocrine system, and gut. Traditional depression treatments all target the brain, with different drugs and/or psychotherapy. Unfortunately, most of the patients have never received any treatment. Studies indicate that gut microbiota could be a direct cause for the disorder. Abnormal microbiota and the microbiota⁻gut⁻brain dysfunction may cause mental disorders, while correcting these disturbance could alleviate depression. Nowadays, the gut microbiota modulation has become a hot topic in treatment research of mental disorders. Depression is closely related with the health condition of the brain⁻gut axis, and maintaining/restoring the normal condition of gut microbiota helps in the prevention/th…

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