肠道菌群失调与多发性硬化

<正>多发性硬化(multiple sclerosis,MS)是一种中枢神经系统慢性炎性自身免疫性疾病,其主要特征是髓鞘降解、轴突脱失和神经元丧失,脑和脊髓发生特征性病变。因此MS患者会出现不同程度的神经功能障碍,如肢体无力、感觉异常、视力模糊和认知缺陷等。目前研究表明遗传、环境及自身免疫等因素是导致MS发生的重要因素~([1])。一、肠道菌群的生理与病理生理功能肠道菌群是人体最大的微生物集群,由肠道中的数万亿微生物组成,包括病毒、细菌和真菌~([2])。肠道菌群在宿主消化、宿主防御、合成维生素以及免疫系统、神经系统的形成等方面具有重要作用,而环境、宿主饮食、免疫系统及神经系统     

肠道菌群与视神经脊髓炎谱系疾病的相关性研究进展

人的肠道菌群是指存在于人体消化道中的一类数量巨大、种类繁多的微生物群,其对人体免疫稳态的建立和免疫系统功能的正常发挥起着极其重要的作用.视神经脊髓炎谱系疾病(NMOSD)是一组病因未明的中枢神经系统自身免疫性炎性脱髓鞘疾病,目前有研究发现肠道菌群可能与NMOSD发病相关.本文就肠道菌群与NMOSD的关系进行综述,以期为...     

肠道菌群和Toll样受体在帕金森病中的研究进展

帕金森病（PD）是以α-突触核蛋白（α-syn）为主要病理特征的第二常见神经退行性疾病。病理性标志物α-syn并不局限于PD患者的黑质致密部,在中枢神经、自主神经及肠神经系统中普遍存在。肠道微生物通过参与免疫、神经内分泌及神经调节实现与大脑之间的双向交流,维持宿主机体平衡和参与疾病的发生。在PD患者中,肠道-脑轴失调引起的胃肠道功能障碍可早于运动障碍10 a发生,提示PD发病起源于肠道传播至大脑。Toll样受体（TLR）在微生物中通过识别病原相关分子模式（PAMP）在先天性免疫中发挥重要作用,该信号的失调参与了α-syn的致病过程。肠道微生物失调对先天性免疫系统的过度刺激和增高肠道屏障的通透性,诱导局部和全身炎症的发生,促进α-syn的传播。本文旨在揭示PD患者肠道-脑轴微生物群与TLR之间的关系,为PD治疗提供新的方向。     

肠道微生物与脑-肠轴的相互作用机制研究进展

脑和肠通过双向神经，内分泌和免疫通讯形成脑-肠轴，二者之间相互影响。肠道微生物 的种类、数量紊乱可以影响肠神经系统（ENS）和中枢神经系统（CNS），脑代谢性疾病及精神障碍也可导致 肠道微生态失衡，从而表明存在微生物-脑-肠轴。微生物-脑-肠轴的提出为研究及治疗中枢神经系 统疾病及功能性胃肠病打开了新的思路。     

肠道微生物与中枢神经系统疾病研究进展

正肠道微生物是人体微生物最大储存库~([1]),时刻与宿主进行着信息交换。微生物及其代谢产物在胎儿时期已对人体产生作用,微生物定植的序贯性、多样性、稳定性及平衡性均会对人体生长发育产生重大影响~([2]),并影响宿主生理病理等多个方面,在人体健康和疾病中起重要作用。本文将对肠道微生物(主要指细菌)与中枢神经系统及其疾病相关性的研究进展进行综述。1肠道微生物对神经系统发育的作用目前研究表明,肠道微生物可以诱导和促进大脑发     

精神分裂症患者的肠-脑轴研究进展

本文目的是探讨肠道微生物、肠-脑轴与精神分裂症的关系,为精神分裂症的治疗开辟新思路。精神分裂症发病机制目前尚未完全阐明,有假说及研究发现,精神分裂症的发生和发展均与病原微生物有关,特别是人体神经系统的肠-脑轴在其中扮演了重要角色。肠道微生物群通过释放和分泌功能性神经递质,影响中枢神经系统的相关神经递质水平,从而改变宿主的情绪、行为和精神状态。本文对近年来关于微生物、肠-脑轴与精神分裂症的研究进展进行综述,讨论肠道细菌与宿主之间的关系。     

肠道菌群对难治性癫痫发病的影响

肠道菌群通过微生物群-肠道-脑轴调节神经功能和行为,并参与多种神经系统疾病的发病机制。癫痫患者肠道菌群结构和功能发生明显变化,但尚未得出一致性变化的菌群。本文概述癫痫患者肠道菌群改变、肠道菌群与癫痫的关系、肠道菌群的抗癫痫作用、微生物群-肠道-脑轴在癫痫发病中潜在机制方面研究进展,以为难治性癫痫提供新的治疗靶点。     

肠道微生物与精神分裂症发病机制相关研究进展北大核心CSCD

精神分裂症是由遗传因素和环境因素共同作用导致的一种慢性精神疾病,其具体病因和发病机制尚不清楚。近年来,微生物-肠-脑轴在精神分裂症中的作用越来越受学界关注。研究表明精神分裂症肠道微生物菌群结构具有多样性,并且肠道微生物可通过免疫炎症反应、代谢通路、神经传导、肠道内分泌系统等多种途径与大脑进行双向信息交流,影响情绪、认知和社交行为。基于此,我们就肠道微生物与精神分裂症发病机制的相关研究作一综述,为探究精神分裂症的病因学、诊断、治疗和预防提供新思路。     

选择性5-羟色胺再摄取抑制剂类抗抑郁药对肠道菌群影响的研究进展

肠道内存在人体最大的微生态环境,对于维持人体的健康发挥着重要作用.近年来,相关研究表明肠道菌群的多样性在抑郁症以及其他精神疾病的发生中起着重要作用.但是肠道菌群在治疗抑郁症中的作用仍有待阐明.现阶段,临床常用的治疗抑郁症的一线药物为选择性5-羟色胺再摄取抑制剂类抗抑郁药(SSRIs),大量动物和临床研究表明SSRIs可...     

白细胞介素、干扰素与精神分裂症关系的研究进展

精神分裂症是重型精神病,反复发作,预后差,目前病因未明.近年来在免疫学理论及新技术的发展下,提示精神分裂症存在免疫功能异常.细胞因子是神经系统和免疫系统之间的重要物质,并参与了神经系统疾患的病理生理过程.现对白细胞介素-1、2、6、10、17及干扰素与精神分裂症之间的关系进行综述.     

Gut, bugs, and brain: role of commensal bacteria in the control of central nervous system disease

The mammalian gastrointestinal track harbors a highly heterogeneous population of microbial organisms that are essential for the complete development of the immune system. The gut microbes or "microbiota," coupled with host genetics, determine the development of both local microbial populations and the immune system to create a complex balance recently termed the "microbiome." Alterations of the gut microbiome may lead to dysregulation of immune responses both in the gut and in distal effector immune sites such as the central nervous system (CNS). Recent findings in experimental autoimmune encephalomyelitis, an animal model of human multiple sclerosis, suggest that altering certain bacterial populations present in the gut can lead to a proinflammatory condition that may result in the development of autoimmune diseases, in particular human multiple sclerosis. In contrast, other commensal bacteria and their antigenic products, when presented in the correct context, can protect against inflammation within the CNS.     

The role of microbiome in central nervous system disorders

Mammals live in a co-evolutionary association with the plethora of microorganisms that reside at a variety of tissue microenvironments. The microbiome represents the collective genomes of these co-existing microorganisms, which is shaped by host factors such as genetics and nutrients but in turn is able to influence host biology in health and disease. Niche-specific microbiome, prominently the gut microbiome, has the capacity to effect both local and distal sites within the host. The gut microbiome has played a crucial role in the bidirectional gut–brain axis that integrates the gut and central nervous system (CNS) activities, and thus the concept of microbiome–gut–brain axis is emerging. Studies are revealing how diverse forms of neuro-immune and neuro-psychiatric disorders are correlated with or modulated by variations of microbiome, microbiota-derived products and exogenous antibiotics and probiotics. The microbiome poises the peripheral immune homeostasis and predisposes host susceptibility to CNS autoimmune diseases such as multiple sclerosis. Neural, endocrine and metabolic mechanisms are also critical mediators of the microbiome–CNS signaling, which are more involved in neuro-psychiatric disorders such as autism, depression, anxiety, stress. Research on the role of microbiome in CNS disorders deepens our academic knowledge about host-microbiome commensalism in central regulation and in practicality, holds conceivable promise for developing novel prognostic and therapeutic avenues for CNS disorders.     

Brain-immune interactions and disease susceptibility

Many studies have established the routes by which the immune and central nervous (CNS) systems communicate. This network of connections permits the CNS to regulate the immune system through both neuroendocrine and neuronal pathways. In turn, the immune system signals the CNS through neuronal and humoral routes, via immune mediators and cytokines. This regulatory system between the immune system and CNS plays an important role in susceptibility and resistance to autoimmune, inflammatory, infectious and allergic diseases. This review focuses on the regulation of the immune system via the neuroendocrine system, and underlines the link between neuroendocrine dysregulation and development of major depressive disorders, autoimmune diseases and osteoporosis.     

Expression and modulation of HLA-DR on cultured human adult astrocytes

Expression of Class II major histocompatibility complex (MHC) antigens on astrocytes has been implicated as contributing to the immune responses characteristic of chronic autoimmune diseases of the central nervous system. We examined the properties and regulation of HLA-DR on cultured human adult astrocytes. We found that a proportion of human astrocytes from each of fifteen individual donors expressed HLA-DR under basal culture condition; while this proportion differed among the human subjects (range 3-65%), the results for each individual remained relatively constant when analyzed at several time points (up to 125 days in vitro). Attempts to modulate HLA-DR expression by a variety of cytokines likely to be present in inflammatory infiltrates in the brain showed that only gamma-interferon could increase the proportion of human astrocytes that expressed HLA-DR. Whether the variability of HLA-DR expression on astrocytes between different individuals reflects a genetic trait which can influence susceptibility to autoimmune central nervous system diseases remains to be determined.     

Neuroimmunology I: Immunoregulation in neurological disease

Aberrations in immune function that ultimately result in disease states may involve three aspects of immune regulation: (1) regulatory T cells, which both suppress and induce immune responses; (2) idiotype-antiidiotype networks, which serve as internal regulatory networks during generation of an immune response; and (3) immune response genes, which determine genetic differences in an individual's immune response. Three major diseases of the nervous system, multiple sclerosis, myasthenia gravis, and acute inflammatory polyneuropathy (Guillain-Barré syndrome), are classified as “autoimmune” in nature and may be due to underlying disorders of immunoregulation. In multiple sclerosis there is a loss of suppressor T cells in the peripheral blood during attacks, in myasthenia gravis there are thymic abnormalities and antibodies against the acetylcholine receptor, and in acute inflammatory polyneuropathy, macrophage-mediated destruction of peripheral nerve myelin occurs in the context of sensitized T cells and is usually associated with a preceding viral illness. In each of these disease the following central questions must be answered: (1) against what antigen (or antigens) of the nervous system is the autoimmune response directed? (2) what is the mechanism of immune damage? and (3) what initiates, or triggers, the autoimmune response?     

The emerging role of probiotics in neurodegenerative diseases: new hope for Parkinson's disease?

Neurodegenerative disease etiology is still unclear, but different contributing factors, such as lifestyle and genetic factors are involved. Altered components of the gut could play a key role in the gut-brain axis, which is a bidirectional system between the central nervous system and the enteric nervous system. Variations in the composition of the gut microbiota and its function between healthy people and patients have been reported for a variety of human disorders comprising metabolic, autoimmune, cancer, and, notably, neurodegenerative disorders. Diet can alter the microbiota composition, affecting the gutbrain axis function. Different nutraceutical interventions have been devoted to normalizing gut microbiome dysbiosis and to improving biological outcomes in neurological conditions, including the use of probiotics. Preclinical and clinical investigations discussed in this review strengthen the correlation between intestinal microbiota and brain and the concept that modifying the microbiome composition may improve brain neurochemistry, modulating different pathways. This review will discuss the potential use of probiotics for Parkinson's disease prevention or treatment or as adjuvant therapy, confirming that gut microbiota modulation influences different pro-survival pathways. Future investigations in Parkinson's disease should consider the role of the gut-brain axis and additional comprehension of the underlying mechanisms is extremely necessary.     

Animal models of immune-mediated neuropathies

PURPOSE OF REVIEW: This article gives an overview on animal models for immune-mediated demyelinating disorders of the peripheral nervous system. As insight into human disease is mainly based on biopsy material and ex-vivo analysis, an understanding of the pathogenetic mechanism of these complex and heterogeneous disorders is mainly based on animal models. RECENT FINDINGS: Besides experimental autoimmune neuritis in rats, recent efforts to establish this model in mice are discussed. In addition, models for spontaneous autoimmune neuropathies and secondary immune reactions in degenerative disorders of the peripheral nervous system are reviewed. SUMMARY: Recently described animal models offer the possibility to analyse the complex interaction of genetic and immunological factors. The entire panel of animal models for immune-mediated disorders of the peripheral nervous system provides a rational basis for studying the mechanisms of pathogenesis and new immunotherapeutic strategies for human autoimmune demyelinating neuropathies.     

The emerging role of probiotics in neurodegenerative diseases: new hope for Parkinson’s disease?

Neurodegenerative disease etiology is still unclear, but different contributing factors, such as lifestyle and genetic factors are involved. Altered components of the gut could play a key role in the gut-brain axis, which is a bidirectional system between the central nervous system and the enteric nervous system. Variations in the composition of the gut microbiota and its function between healthy people and patients have been reported for a variety of human disorders comprising metabolic, autoimmune, cancer, and, notably, neurodegenerative disorders. Diet can alter the microbiota composition, affecting the gut-brain axis function. Different nutraceutical interventions have been devoted to normalizing gut microbiome dysbiosis and to improving biological outcomes in neurological conditions, including the use of probiotics. Preclinical and clinical investigations discussed in this review strengthen the correlation between intestinal microbiota and brain and the concept that modifying the microbiome composition may improve brain neurochemistry, modulating different pathways. This review will discuss the potential use of probiotics for Parkinson’s disease prevention or treatment or as adjuvant therapy, confirming that gut microbiota modulation influences different pro-survival pathways. Future investigations in Parkinson’s disease should consider the role of the gut-brain axis and additional comprehension of the underlying mechanisms is extremely necessary.     

Role of vitamin D in immune responses and autoimmune diseases, with emphasis on its role in multiple sclerosis

Vitamin D is a seco-steroid involved in calcium and phosphorus metabolism, and bone formation and mineralization, through binding to a specific nuclear receptor, vitamin D receptor (VDR). Besides its well-established functions on bone health, multiple lines of evidence have indicated the immunomodulatory roles of vitamin D. Vitamin D can affect both innate and adaptive immunity, and prevent autoimmune responses efficiently. Vitamin D regulates the immune responses by suppressing T cell proliferation and modulating macrophage functions. Epidemiological studies have shown that vitamin D deficiency is associated with multiple diseases such as rickets and cancer. Moreover, associations between vitamin D and autoimmune diseases have been confirmed in multiple sclerosis (MS), rheumatoid arthritis (RA), etc. The present review mainly summarized the recent findings on the immunomodulatory role of vitamin D in various disorders, with special focus on its role in MS, an autoimmune disease of the nervous system.