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。     

肠道菌群与中枢神经系统疾病及粪便微生物群移植的治疗应用前景

<正>肠道是人体中最大的微生物群落,肠道菌群调节宿主许多过程,包括新陈代谢、炎症和免疫反应,相反,宿主通过内外环境调节肠道菌群的组成和数量,这种宿主和菌群之间的复杂的相互作用对人体健康和功能至关重要。然而,当宿主与肠道菌群之间的共生关系被破坏时,可能导致或促进疾病~([1])。本文回顾肠道菌群与宿主中枢神经系统的相互作用,讨论肠道菌群与常见中枢神经系统疾病之间的可能联系,最后提出通过纠正菌群失调以预防和治疗疾病的潜在方法。     

肠道微生物与常见中枢神经系统疾病相关性的研究进展

肠道微生物不仅局限作用于胃肠道,可以通过脑肠轴对大脑功能产生重要影响.肠道微生物结构与功能的改变与阿茨海默病、帕金森病、多发性硬化、脑卒中等一系列常见中枢神经系统疾病密切相关,通过改善肠道微生物的微生态疗法有望成为预防和治疗中枢神经系统疾病的有效途径.现对近年来肠道微生物与常见中枢神经系统疾病的相关研究进展进行综述.     

粪菌移植治疗中枢神经系统疾病的研究进展

中枢神经系统疾病除了神经系统相关症状外，常伴随胃肠道症状，在不同疾病患者体内可观察到相应肠道菌群失调现象。肠道菌群及代谢产物可通过外周神经、免疫等途径参与中枢神经系统活动，肠道菌群失调与阿尔兹海默病、帕金森病、肌萎缩性脊髓侧索硬化、多发性硬化等多种中枢神经系统疾病的发生发展密切相关，有研究证明，模型动物或患者在接受粪菌移植治疗后症状改善。该文就粪菌移植治疗中枢神经系统疾病中的研究进展进行综述。     

从脾分期辨证论治帕金森病：丁氏内科程门雪流派学术思想的应用

近年来的研究发现,肠道菌群失调可能与帕金森病的发病和病程进展密切相关,无论是在帕金森病的临床前期还是早期、中期和晚期阶段,对患者的肠道菌群进行调节,都可能给帕金森病的治疗带来新的契机。肠道菌群失调与帕金森病发病之间的相关性与丁氏内科程门雪流派学术思想传承人蔡淦教授从脾分期辨证论治帕金森病的理论不谋而合。基于该理论,采用从脾论治基本方化裁,分期辨证论治帕金森病取得了令人满意的疗效,为中西医结合治疗帕金森病等神经退行性疾病提供了实证性依据。     

益生菌防治抑郁症的研究进展

益生菌是人体肠道微生态正常菌群的重要组成部分,对维持肠道微生态平衡和人体健康起重要作用。近期越来越多的研究表明,抑郁症与肠道菌群失调有关,调节肠道菌群平衡可能对认知和情绪的改善大有裨益。随之,益生菌在防治焦虑抑郁等疾病方面的作用也引起了国内外学者的高度重视,有可能为我们治疗抑郁症提供新的思路和方向。本文就目前益生菌在抑郁症方面的相关研究进行综述,旨在为进一步研究开发益生菌提供参考依据。     

常见精神障碍的脑肠轴机制研究进展和临床干预

人体肠道拥有大量且种类丰富的微生物群,在机体的多项生理过程中扮演着重要角色。已有研究发现肠道微生物通过脑-肠轴机制可以作用于脑疾病的发生。本文目的是通过对肠道微生物在精神分裂症、双相情感障碍及抑郁症中的作用机制进行述评,为精神障碍的预防与治疗提供新的思路。     

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     

降钙素基因相关肽对中枢神经系统的影响

降钙素基因相关肽(CGRP)是一种新型的内源性生物活性神经多肽,它广泛分布于中枢神经系统(CNS),并对其产生多种影响。研究表明,CGRP能扩张脑血管、对损伤的神经元具有保护和功能恢复、参与伤害性信息感受、介导神经-免疫系统相互调节等。此外,CGRP也能对癫痫疾病产生影响。深入研究CGRP对CNS的影响,对揭示脑部某些疾病的发生、发展规律,进而提出新的诊断措施和开发新的治疗思路,可能提供有益的帮助。     

Parasitic diseases in the central nervous system]

Along with the drastic decrease of soil-transmitted intestinal helminthiases, parasitic diseases in general are ignored, or considered as the disease of the past, in Japan. However, due to the Japanese food culture of eating raw materials, food-borne parasitic diseases are still present in Japan. The majority of food-borne parasitic diseases are zoonotic, and caused by ectopic migration of parasite larvae. They accidentally migrate into CNS to cause deleterious conditions. Clinicians should always remind about the possibility of parasitic diseases when they make differential diagnosis for CNS diseases.     

Ginsenosides and their CNS targets

Ginsenosides are a special group of triterpenoid saponins attributed to medical effects of ginseng. Therefore, they have been research targets over the last three decades to explain ginseng actions and a wealth of literature has been presented reporting on ginsenosides' effects on the human body. Recently, there is increasing evidence on beneficial effects of ginsenosides to the central nervous system (CNS). Using a wide range of in vitro and in vivo models, researchers have attributed these effects to specific pharmacological actions of ginsenosides on cerebral metabolism, oxidative stress and radical formation, neurotransmitter imbalance and membrane stabilizing effects, and even antiapoptotic effects. Modulating these particular mechanisms by ginsenosides has thus been reported to exert either general stimulatory effects on the brain functions or protecting the CNS against various disease conditions. In this review, we try to address the recently reported ginsenosides' actions on different CNS targets particularly those supporting possible therapeutic efficacies in CNS disorders and neurodegenerative diseases.     

Tissue inhibitor of metalloproteinase (TIMP)-1: the TIMPed balance of matrix metalloproteinases in the central nervous system

Astrocytes are intimately involved in the mechanisms of neural injury and repair. They participate in a variety of homeostatic functions and elicit repair responses as balance mechanisms. Currently, there is a growing appreciation of a more active role of astrocytes in neuronal signaling and function. One key homeostatic mechanism of astrocytes in tissue repair is maintained through their production of tissue inhibitors of metalloproteinases (TIMPs). The family of TIMPs (1-4) plays a central regulatory role as inhibitors of matrix metalloproteinases (MMPs), enzymes involved in extracellular matrix maintenance and remodeling. Recently, TIMP-1, the inducible form, has been identified as a multifunctional molecule with divergent functions. It participates in wound healing and regeneration, cell morphology and survival, tumor metastasis, angiogenesis, and inflammatory responses. An imbalance of MMP/TIMP regulation has been implicated in several inflammatory diseases of the central nervous system (CNS). Here we review the conundrums of TIMP-1 regulation in CNS pathophysiology. We propose that astrocyte-TIMP-1 may play an important role in CNS homeostasis and disease. Astrocyte TIMP-1 expression is differentially regulated in inflammatory neurodegenerative diseases and may have significant therapeutic relevance.     

Cell-to-cell transmission of non-prion protein aggregates

Neurodegenerative disorders such as Alzheimer disease, Parkinson disease, frontotemporal dementia, Huntington disease and Creutzfeldt-Jakob disease (CJD) are characterized by progressive accumulation of protein aggregates in selected brain regions. Protein misfolding and templated assembly into aggregates might result from an imbalance between protein synthesis, aggregation and clearance. Although protein misfolding and aggregation occur in most neurodegenerative disorders, the concept of spreading and infectivity of aggregates in the CNS has, until now, been confined to prion diseases such as CJD and bovine spongiform encephalopathy. Emerging evidence, however, suggests that prion-like spreading, involving secreted proteins such as amyloid-β and cytosolic proteins such as tau, huntingtin and α-synuclein, can occur in other neurodegenerative disorders. The underlying molecular mechanisms and the therapeutic implications of the new data are discussed in this article.     

Somatostatin and Alzheimer's disease: a hypothesis

Summary Recent data suggest a disturbance of some brain somatostatin neurons in Alzheimer's disease. Moreover, some endocrine activities known to be regulated by somatostatin, such as growth hormone, thyroid-stimulating-hormone, somatomedins, as well as insulin and glucose metabolism, also seem to be affected in some patients. It is speculated that these changes are due to a global CNS and endocrine somatostatin defect in Alzheimer's disease and that the described endocrine imbalance may indirectly be responsible for at least part of the CNS pathology.     

Use of gene therapy in central nervous system repair

Recent advances have increased our molecular understanding of the central nervous system (CNS), in both health and disease. In order to realize the clinical benefits of these findings, new molecular-based therapies need to be developed, such as CNS gene therapy. Although the field has suffered setbacks, it remains an attractive technology for providing new therapies in the post-genomic world. The development of new vectors, and their extensive application in animal models of CNS disease, provides evidence suggesting that gene therapy will eventually become an accepted clinical option. In fact, the first gene therapy clinical trial for Parkinson's disease has recently begun. This review discusses how gene therapy has been applied in animal models, and how it may be used to repair the damage caused by CNS diseases and trauma in human beings. Furthermore, it explores how such treatments may be combined with, and augment, more conventional therapeutic approaches.     

Commensal gut flora and brain autoimmunity: a love or hate affair?

Multiple sclerosis (MS) and other chronic inflammatory autoimmune diseases represent major public health challenges in industrialised Western society. MS results from an autoimmune attack against myelin structures by self-reactive lymphocytes, which are normal components of the healthy immune repertoire. The nature of the triggers that convert the innocuous self-reactive lymphocytes into an autoaggressive phenotype is poorly understood. In the past, it was primarily suspected that pathogenic infections trigger MS. However, so far, none of the incriminated pathogenic microbes were firmly associated with the disease. A growing body of evidence in animal models of MS implicates the gut microbiota in the induction of central nervous system (CNS) autoimmunity. The mammalian gut harbors a diverse population of microbial organisms which are essential for our well being. There is an increasing understanding that the gut microbiota not only modulates the local immune functions but also affects the systemic immune system. We are only just beginning to understand the nature of the interactions of the gut microbiota with the host’s immune system especially in the context of autoimmune diseases. This review will address the influence of intestinal microbiota on immune homeostasis and on the development of autoimmune responses at sites distal to the intestine with a particular emphasis placed on a discussion about CNS autoimmunity.     

A Rose by Any Other Name? The Potential Consequences of Microglial Heterogeneity During CNS Health and Disease

Microglial activation and macrophage infiltration into the CNS are common features of CNS autoimmune disease and of chronic neurodegenerative diseases. Because these cells largely express an overlapping set of common macrophage markers, it has been difficult to separate their respective contributions to disease onset and progression. This problem is further confounded by the many types of macrophages that have been termed microglia. Several approaches, ranging from molecular profiling of isolated cells to the generation of irradiation chimeric rodent models, are now beginning to generate rudimentary definitions distinguishing the various types of microglia and macrophages found within the CNS and the potential roles that these cells may play in health and disease.     

Patterns and significance of concomitant central and peripheral inflammatory demyelination

Inflammatory demyelinating diseases comprise a spectrum of disorders that affect central nervous system (CNS) and peripheral nervous system (PNS) myelin. Most individuals have demyelinating disease restricted to one or the other compartment but patients with concomitant CNS and PNS inflammatory inflammatory demyelinating processes have been reported not infrequently. In most such patients, involvement of either the CNS or the PNS predominates the clinical picture. Involvement of the other compartment is usually mild or subclinical with unclear prognostic and therapeutic implications. Similarly, while experimentally induced demyelinating disease in animal models is usually CNS or PNS predominant, varying degrees of pathology in the other system can occur depending on the species, type of immunogen, and genetic background of the immunized animal. When CNS and PNS demyelinating diseases occur concurrently, effective treatment for CNS disease can be safely combined with effective treatment for PNS disease.     

Transplantation of glial-committed progenitor cells into a viral model of multiple sclerosis induces remyelination in the absence of an attenuated inflammatory response

Transplantation of remyelination-competent cells represents a promising strategy for the treatment of demyelinating diseases. As the environment dictates the success or failure of remyelination, it is critical to understand the role that the immune system plays in transplant-mediated remyelination. In this study, we evaluated the severity of neuroinflammation following transplantation of glial-committed progenitor cells into the spinal cords of mice chronically infected with mouse hepatitis virus (MHV), a model in which T cells and macrophages are critical in amplifying the severity of demyelination. Transplantation was performed following viral persistence in which inflammation and demyelination are established and clinical disease is evident. Mice were sacrificed 10 and 21 days following progenitor cell transplantation and the effect on neuroinflammation evaluated. Treatment did not alter accumulation of T cells or macrophages within the CNS as compared to control mice. Moreover, progenitor cell implantation did not affect local cytokine/chemokine gene expression in the CNS. Finally, remyelination associated with transplantation did not result in an imbalance of T(H)1-associated cytokine production by virus-specific T cells. These studies demonstrate that progenitor cell-mediated remyelination is not the result of modulating the composition of the cellular infiltrate nor cytokine expression by virus-specific T cells and suggest that remyelination may not depend on amelioration of the inflammatory response or alteration of cytokine secretion by virus-specific T cells.