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Protein & Cell Oct 2023The gut microbiota has been found to interact with the brain through the microbiota-gut-brain axis, regulating various physiological processes. In recent years, the... (Review)
Review
The gut microbiota has been found to interact with the brain through the microbiota-gut-brain axis, regulating various physiological processes. In recent years, the impacts of the gut microbiota on neurodevelopment through this axis have been increasingly appreciated. The gut microbiota is commonly considered to regulate neurodevelopment through three pathways, the immune pathway, the neuronal pathway, and the endocrine/systemic pathway, with overlaps and crosstalks in between. Accumulating studies have identified the role of the microbiota-gut-brain axis in neurodevelopmental disorders including autism spectrum disorder, attention deficit hyperactivity disorder, and Rett Syndrome. Numerous researchers have examined the physiological and pathophysiological mechanisms influenced by the gut microbiota in neurodevelopmental disorders (NDDs). This review aims to provide a comprehensive overview of advancements in research pertaining to the microbiota-gut-brain axis in NDDs. Furthermore, we analyzed both the current state of research progress and discuss future perspectives in this field.
Topics: Humans; Brain-Gut Axis; Autism Spectrum Disorder; Brain; Gastrointestinal Microbiome; Neurodevelopmental Disorders
PubMed: 37166201
DOI: 10.1093/procel/pwad026 -
The Korean Journal of Gastroenterology... Apr 2023Patients frequently report that stress causes or exacerbates gastrointestinal (GI) symptoms, indicating a functional relationship between the brain and the GI tract. The... (Review)
Review
Patients frequently report that stress causes or exacerbates gastrointestinal (GI) symptoms, indicating a functional relationship between the brain and the GI tract. The brain and GI tract are closely related embryologically and functionally, interacting in various ways. The concept of the brain-gut axis was originally established in the 19th and early 20th centuries based on physiological observations and experiments conducted in animals and humans. In recent years, with the growing recognition that gut microbiota plays a vital role in human health and disease, this concept has been expanded to the brain-gut-microbiota axis. The brain influences the motility, secretion, and immunity of the GI tract, with consequent effects on the composition and function of the gut microbiota. On the other hand, gut microbiota plays an essential role in the development and function of the brain and enteric nervous system. Although knowledge of the mechanisms through which the gut microbiota influences distant brain function is incomplete, studies have demonstrated communication between these organs through the neuronal, immune, and endocrine systems. The brain-gut-microbiota axis is an essential aspect of the pathophysiology of functional GI disorders such as irritable bowel syndrome, and is also involved in other GI diseases, including inflammatory bowel disease. This review summarizes the evolving concept of the brain-gut-microbiota axis and its implications for GI diseases, providing clinicians with new knowledge to apply in clinical practice.
Topics: Animals; Humans; Brain-Gut Axis; Microbiota; Gastrointestinal Diseases; Brain
PubMed: 37096434
DOI: 10.4166/kjg.2023.028 -
Frontiers in Immunology 2021The gut-brain axis refers to the bidirectional communication between the gut and brain, and regulates intestinal homeostasis and the central nervous system neural... (Review)
Review
The gut-brain axis refers to the bidirectional communication between the gut and brain, and regulates intestinal homeostasis and the central nervous system neural networks and neuroendocrine, immune, and inflammatory pathways. The development of sequencing technology has evidenced the key regulatory role of the gut microbiota in several neurological disorders, including Parkinson's disease, Alzheimer's disease, and multiple sclerosis. Epilepsy is a complex disease with multiple risk factors that affect more than 50 million people worldwide; nearly 30% of patients with epilepsy cannot be controlled with drugs. Interestingly, patients with inflammatory bowel disease are more susceptible to epilepsy, and a ketogenic diet is an effective treatment for patients with intractable epilepsy. Based on these clinical facts, the role of the microbiome and the gut-brain axis in epilepsy cannot be ignored. In this review, we discuss the relationship between the gut microbiota and epilepsy, summarize the possible pathogenic mechanisms of epilepsy from the perspective of the microbiota gut-brain axis, and discuss novel therapies targeting the gut microbiota. A better understanding of the role of the microbiota in the gut-brain axis, especially the intestinal one, would help investigate the mechanism, diagnosis, prognosis evaluation, and treatment of intractable epilepsy.
Topics: Animals; Brain; Brain-Gut Axis; Epilepsy; Gastrointestinal Microbiome; Humans; Neuroimmunomodulation
PubMed: 34707612
DOI: 10.3389/fimmu.2021.742449 -
Frontiers in Endocrinology 2022The discovery of kisspeptin as a critical central regulatory factor of GnRH release has given people a novel understanding of the neuroendocrine regulation in human... (Review)
Review
The discovery of kisspeptin as a critical central regulatory factor of GnRH release has given people a novel understanding of the neuroendocrine regulation in human reproduction. Kisspeptin activates the signaling pathway by binding to its receptor kisspeptin receptor (KISS1R) to promote GnRH secretion, thereby regulating the hypothalamic-pituitary-gonadal axis (HPG) axis. Recent studies have shown that kisspeptin neurons located in arcuate nucleus (ARC) co-express neurokinin B (NKB) and dynorphin (Dyn). Such neurons are called KNDy neurons. KNDy neurons participate in the positive and negative feedback of estrogen to GnRH secretion. In addition, kisspeptin is a key factor in the initiation of puberty, and also regulates the processes of female follicle development, oocyte maturation, and ovulation through the HPG axis. In male reproduction, kisspeptin also plays an important role, getting involved in the regulation of Leydig cells, spermatogenesis, sperm functions and reproductive behaviors. Mutations in the gene or disorders of the kisspeptin/KISS1R system may lead to clinical symptoms such as idiopathic hypogonadotropic hypogonadism (iHH), central precocious puberty (CPP) and female infertility. Understanding the influence of kisspeptin on the reproductive axis and related mechanisms will help the future application of kisspeptin in disease diagnosis and treatment. In this review, we critically appraise the role of kisspeptin in the HPG axis, including its signaling pathways, negative and positive feedback mechanisms, and its control on female and male reproduction.
Topics: Female; Gonadotropin-Releasing Hormone; Humans; Kisspeptins; Male; Receptors, Kisspeptin-1; Reproduction; Semen
PubMed: 35837314
DOI: 10.3389/fendo.2022.925206 -
Biomedicine & Pharmacotherapy =... Jul 2022Approximately, one in three ischemic stroke survivors suffered from depression, namely, post-stroke depression (PSD). PSD affects functional rehabilitation and may lead... (Review)
Review
Approximately, one in three ischemic stroke survivors suffered from depression, namely, post-stroke depression (PSD). PSD affects functional rehabilitation and may lead to poor quality of life of patients. There are numerous explanations about the etiologies of PSD. Here, we speculated that PSD are likely to be the result of specific changes in brain pathology. We hypothesized that the stroke-induced hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis plays an important role in PSD. Stroke initiates a complex sequence of events in neuroendocrine system including HPA axis. The HPA axis is involved in the pathophysiology of depression, especially, the overactivity of the HPA axis occurs in major depressive disorder. This review summarizes the possible etiologies of PSD, focusing on the stroke-induced activation of HPA axis, mainly including the stress followed by severe brain damage and the proinflammatory cytokines release. The role of hyperactive of HPA axis in PSD was discussed in detail, which includes the role of high level corticotropin-releasing hormone in PSD, the effects of glucocorticoids on the alterations in specific brain structures, the expression of enzymes, excitotoxicity, the change in intestinal permeability, and the activation of microglia. The relationship between neuroendocrine regulation and inflammation was also described. Finally, the therapy of PSD by regulating HPA axis, neuroendocrine, and immunity was discussed briefly. Nevertheless, the change of HPA axis and the occurring of PSD maybe interact and promote on each other, and future investigations should explore this hypothesis in more depth.
Topics: Depression; Depressive Disorder, Major; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Quality of Life; Stroke
PubMed: 35643064
DOI: 10.1016/j.biopha.2022.113146 -
Nutrients May 2022Depression is a kind of worldwide mental illness with the highest morbidity and disability rate, which is often accompanied by gastrointestinal symptoms. Experiments... (Review)
Review
Depression is a kind of worldwide mental illness with the highest morbidity and disability rate, which is often accompanied by gastrointestinal symptoms. Experiments have demonstrated that the disorder of the intestinal microbial system structure plays a crucial role in depression. The gut-brain axis manifests a potential linkage between the digestion system and the central nervous system (CNS). Nowadays, it has become an emerging trend to treat diseases by targeting intestinal microorganisms (e.g., probiotics) and combining the gut-brain axis mechanism. Combined with the research, we found that the incidence of depression is closely linked to the gut microbiota. Moreover, the transformation of the gut microbiota system structure is considered to have both positive and negative regulatory effects on the development of depression. This article reviewed the mechanism of bidirectional interaction in the gut-brain axis and existing symptom-relieving measures and antidepression treatments related to the gut microbiome.
Topics: Brain-Gut Axis; Depression; Gastrointestinal Microbiome; Microbiota; Probiotics
PubMed: 35631224
DOI: 10.3390/nu14102081 -
Seminars in Immunology Sep 2023The multifaceted microbiota characterizing our gut plays a crucial role in maintaining immune, metabolic and tissue homeostasis of the intestine as well as of distal... (Review)
Review
The multifaceted microbiota characterizing our gut plays a crucial role in maintaining immune, metabolic and tissue homeostasis of the intestine as well as of distal organs, including the central nervous system. Microbial dysbiosis is reported in several inflammatory intestinal diseases characterized by the impairment of the gut epithelial and vascular barriers, defined as leaky gut, and it is reported as a potential danger condition associated with the development of metabolic, inflammatory and neurodegenerative diseases. Recently, we pointed out the strict connection between the gut and the brain via a novel vascular axis. Here we want to deepen our knowledge on the gut-brain axis, with particular emphasis on the connection between microbial dysbiosis, leaky gut, cerebral and gut vascular barriers, and neurodegenerative diseases. The firm association between microbial dysbiosis and impairment of the vascular gut-brain axis will be summarized in the context of protection, amelioration or boosting of Alzheimer, Parkinson, Major depressive and Anxiety disorders. Understanding the relationship between disease pathophysiology, mucosal barrier function and host-microbe interaction will foster the use of the microbiome as biomarker for health and disease as well as a target for therapeutic and nutritional advances.
Topics: Humans; Brain-Gut Axis; Neuroinflammatory Diseases; Gastrointestinal Microbiome; Dysbiosis; Depressive Disorder, Major; Brain
PubMed: 37422929
DOI: 10.1016/j.smim.2023.101802 -
Frontiers in Endocrinology 2023Cognitive function in humans depends on the complex and interplay between multiple body systems, including the hypothalamic-pituitary-adrenal (HPA) axis. The gut... (Review)
Review
Cognitive function in humans depends on the complex and interplay between multiple body systems, including the hypothalamic-pituitary-adrenal (HPA) axis. The gut microbiota, which vastly outnumbers human cells and has a genetic potential that exceeds that of the human genome, plays a crucial role in this interplay. The microbiota-gut-brain (MGB) axis is a bidirectional signalling pathway that operates through neural, endocrine, immune, and metabolic pathways. One of the major neuroendocrine systems responding to stress is the HPA axis which produces glucocorticoids such as cortisol in humans and corticosterone in rodents. Appropriate concentrations of cortisol are essential for normal neurodevelopment and function, as well as cognitive processes such as learning and memory, and studies have shown that microbes modulate the HPA axis throughout life. Stress can significantly impact the MGB axis the HPA axis and other pathways. Animal research has advanced our understanding of these mechanisms and pathways, leading to a paradigm shift in conceptual thinking about the influence of the microbiota on human health and disease. Preclinical and human trials are currently underway to determine how these animal models translate to humans. In this review article, we summarize the current knowledge of the relationship between the gut microbiota, HPA axis, and cognition, and provide an overview of the main findings and conclusions in this broad field.
Topics: Animals; Humans; Gastrointestinal Microbiome; Hypothalamo-Hypophyseal System; Brain; Hydrocortisone; Pituitary-Adrenal System; Cognition
PubMed: 37404311
DOI: 10.3389/fendo.2023.1130689 -
Progress in Neuro-psychopharmacology &... Aug 2020Accumulating evidence indicates that patients with severe mental disorders, including major depression, bipolar disorder and schizophrenia present with various... (Review)
Review
Accumulating evidence indicates that patients with severe mental disorders, including major depression, bipolar disorder and schizophrenia present with various alterations of the gut microbiota and increased intestinal permeability. In addition, the hypothalamic-pituitary-adrenal (HPA) axis dysregulation and subclinical inflammation have been reported in this group of patients. Although it has been found that the HPA axis dysregulation appears as a consequence of psychosocial stress, especially traumatic life events, the exact mechanisms of this observation remain unclear. Animal model studies have unraveled several mechanisms linking the gut microbiota with the HPA axis dysfunction. Indeed, the gut microbiota can activate the HPA axis through several mediators that cross the blood-brain barrier and include microbial antigens, cytokines and prostaglandins. There is also evidence that various microbial species can affect ileal corticosterone production that may impact the activity of the HPA axis. However, some metabolites released by various microbes, e.g., short-chain fatty acids, can attenuate the HPA axis response. Moreover, several bacteria release neurotransmitters that can directly interact with vagal afferents. It has been postulated that the HPA axis activation can impact the gut microbiota and intestinal permeability. In this article, we discuss various mechanisms linking the gut microbiota with the HPA axis activity and summarize current evidence for a cross-talk between the gut-brain axis and the HPA axis from studies of patients with mood and psychotic disorders. Finally, we show potential clinical implications that can arise from future studies investigating the HPA axis activity with respect to the gut microbiota in severe mental disorders.
Topics: Gastrointestinal Microbiome; Humans; Hypothalamo-Hypophyseal System; Mental Disorders; Pituitary-Adrenal System
PubMed: 32335265
DOI: 10.1016/j.pnpbp.2020.109951 -
Frontiers in Cellular and Infection... 2023The microbiota gut brain (MGB) axis has been shown to play a significant role in the regulation of inflammatory and infective diseases. Exploring the structure and... (Review)
Review
The microbiota gut brain (MGB) axis has been shown to play a significant role in the regulation of inflammatory and infective diseases. Exploring the structure and communication mode of MGB axis is crucial for understanding its role in diseases, and studying the signaling pathways and regulatory methods of MGB axis regulation in diseases is also of profound significance for future clinical research. This article reviews the composition, communication mechanism of MGB axis and its role in inflammatory and infective diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), autism spectrum disorder (ASD), depression, psoriasis, irritable bowel syndrome (IBS), and inflammatory bowel diseases (IBD). In addition, our investigation delved into the regulatory functions of the inflammasome, IFN-I, NF-κB, and PARK7/DJ-1 innate immune signaling pathway in the context of inflammatory and infective diseases. Ultimately, we discussed the efficacy of various interventions, including fecal microbiota transplantation (FMT), antibiotics, probiotics, prebiotics, synbiotics, and postbiotics, in the management of inflammatory and infective diseases. Understanding the role and mechanism of the MGB axis might make positive effects in the treatment of inflammatory and infective diseases.
Topics: Humans; Brain-Gut Axis; Autism Spectrum Disorder; Gastrointestinal Microbiome; Probiotics; Immunity, Innate; Communicable Diseases; Brain
PubMed: 37868345
DOI: 10.3389/fcimb.2023.1282431