肠道微生物在神经系统自身免疫性疾病中的研究进展

肠道微生物是人体最直接的外环境,对维持健康具有重要作用.肠道微生物可维持人体免疫系统稳态,与宿主共生可影响人体营养、代谢和免疫功能.肠道微生物通过免疫系统和内分泌系统与神经系统产生双向联系,即微生物-肠-脑轴.肠道微生物失调引起神经系统及外周异常免疫反应,参与自身免疫性疾病的发病机制.本文综述肠道微生物在多发性硬化、视...     

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。     

肠道微生物与阿尔茨海默病发生相关性的研究进展

阿尔茨海默病(AD)以进行性认知功能障碍为特征,是最常见的痴呆类型。近年来,肠道菌群作为寄居在人消化道内的大量微生物,成为研究众多疾病发病机制的热点之一。越来越多的证据表明,肠道微生物通过肠－脑轴与中枢神经系统功能沟通,影响宿主的认知行为,与AD的发生发展密切相关。研究发现,AD动物模型和患者的肠道内微生物群多样性降低。肠道微生物可通过产生肠道代谢产物、神经递质影响宿主大脑神经生化过程,从而增加或降低宿主患AD的风险。部分肠道微生物可驱动外周炎症,进而激活脑内神经胶质和炎症因子,诱发神经毒性反应,最终加速AD的发生发展。该文综述了肠道微生物与AD的相互作用机制,并探讨益生菌对AD防治的潜在价值,以期为AD的预防及治疗提供新思路。 [引用格式:国际神经病学神经外科学杂志, 2021, 48(4): 377-381.]     

微生物-肠-脑轴与孤独症谱系障碍研究进展

孤独症谱系障碍（ASD）是一种严重神经发育性障碍，是遗传因素和环境因素共同作用的 结果。近年来，越来越多的证据支持肠道内的微生物通过肠-脑轴影响脑发育，并产生相应的行为表现 型。肠道微生物失调和ASD的关系也日益受到重视，可能参与了部分ASD的发生与发展。现综述微生物- 肠-脑轴与ASD 间的关系。     

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。     

肠道菌群在强迫症治疗中的研究进展

强迫症是一种病因未明的致残性精神障碍, 其发生发展过程与肠道菌群的关联尚未被完全阐明。虽然强迫症的确切发病机制尚不清楚, 但现有证据表明脑肠轴通过免疫炎症、神经递质及内分泌等多条通路参与强迫症的发生发展。本文综述了肠道微生物群参与强迫症病理生理学的新证据及其作为新的治疗手段的潜力, 同时总结了目前脑肠轴研究的主要研究方法和不足。探讨了益生菌和粪便移植等微生物重组策略在强迫症治疗中的潜力和挑战, 并对未来的研究方向进行了展望, 期待通过对脑肠轴的深入研究能够为强迫症的防治提供新的靶点和方向。     

精神分裂症患者肠道菌群失调对认知功能受损的影响

本文目的是综述精神分裂症患者肠道菌群失调对认知功能受损的影响,为改善精神分裂症患者认知功能受损情况的新方法提供参考。精神分裂症患者的认知功能受损普遍存在,是阻碍其重返社会的重要原因之一。随着肠道菌群-肠-脑轴概念的提出,许多研究者发现精神分裂症患者肠道菌群失调与认知功能受损存在一定联系,本文阐述并总结既往研究中发现的此种联系,以期为改善精神分裂症患者认知功能受损情况提供参考。     

5-HT对情绪和认知的影响与脑肠轴的关系研究

<正>脑肠轴(brain-gut axis)是中枢神经系统(central nervous system,CNS)和胃肠道之间的双向通讯系统,5-羟色胺(5-hydroxytryptamine,5-HT)是脑肠轴中关键的神经递质。同时,肠道菌群及其代谢产物不仅维持CNS的正常发育,而且也参与了神经精神疾病和身心疾病的病理过程,甚至影响个体社交和认知功能。受肠道菌群影响的行为与5-HT能神经传递的行为之间也存在实质性重叠,肠道菌群多样性和稳定性的下降可能决定了人类5-HT相关的健康问题。所以本文通过5-HT与脑肠轴沟通,详细阐述其影响人类情绪和认知的机制和途径。     

益生菌治疗心境障碍机制的研究进展

近年来,心境障碍患者的肠道菌群紊乱逐渐受到人们的关注。肠道菌群经微生物 - 肠 - 脑（MGB）轴沟通中枢神经系统实现双向调节,影响人的认知、情绪和行为。益生菌及其产物重塑肠道 微生态,改善免疫和内分泌系统功能,恢复神经递质水平。因此,应用益生菌调节失衡的肠道菌群,恢 复紊乱的 MGB 轴正成为心境障碍的辅助疗法。但目前益生菌疗法仍存在一些问题,如菌株之间的差异 性、肠道菌群组成的异质性等。未来需要进行更多试验以明确不同菌株作用机制,从而对不同亚型心 境障碍患者针对性地使用益生菌,完善治疗策略。     

Exploring interactions between xenobiotics,microbiota, and neurotoxicity in zebrafish

Susceptibility to xenobiotic exposures is variable. One factor that might account for this is the microbiome, which encompasses all microorganisms, their encoded genes, and associated functions that colonize a host organism. Microbiota harbor the capacity to affect the toxicokinetics and toxicodynamics of xenobiotic exposures. The neurotoxicological effects of environmental chemicals may be modified by intestinal microbes via the microbiota-gut-brain axis. This is a complex, bi-directional signaling pathway between intestinal microbes and the host nervous system. As a model organism, zebrafish are extremely well-placed to illuminate mechanisms by which microbiota modify the developmental neurotoxicity of environmental chemicals. The goal of this review article is to examine the microbiota-gut-brain axis in a toxicological context, specifically focusing on the strengths and weaknesses of the zebrafish model for the investigation of interactions between xenobiotic agents and host-associated microbes. Previous studies describing the relationship between intestinal microbes and host neurodevelopment will be discussed. From a neurotoxicological perspective, studies utilizing zebrafish to assess links between neurotoxicological outcomes and the microbiome are emphasized. Overall, there are major gaps in our understanding the mechanisms by which microbiota interact with xenobiotics to cause or modify host neurotoxicity. In this review, we demonstrate that zebrafish are an ideal model system for studying the complex relationship between chemical exposures, microorganisms, and host neurotoxicological outcomes.     

Harnessing Gut Microbes for Mental Health: Getting From Here to There

There has been an explosion of interest in the study of microorganisms inhabiting the gastrointestinal tract (gut microbiota) and their impact on host health and physiology. Accumulating data suggest that altered communication between gut microbiota and host systems could participate in disorders such as obesity, diabetes mellitus, and autoimmune disorders as well as neuropsychiatric disorders, including autism, anxiety, and major depressive disorders. The conceptual development of the microbiome-gut-brain axis has facilitated understanding of the complex and bidirectional networks between gastrointestinal microbiota and their host, highlighting potential mechanisms through which this environment influences central nervous system physiology. Communication pathways between gut microbiota and the central nervous system could include autonomic, neuroendocrine, enteric, and immune systems, with pathology resulting in disruption to neurotransmitter balance, increases in chronic inflammation, or exacerbated hypothalamic-pituitary-adrenal axis activity. However, uncertainty remains regarding the generalizability of controlled animal studies to the more multifaceted pattern of human pathophysiology, especially with regard to the therapeutic potential for neuropsychiatric health. This narrative review summarizes current understanding of gut microbial influence over physiological function, with an emphasis on neurobehavioral and neurological impairment based on growing understanding of the gut-brain axis. Experimental and clinical data regarding means of therapeutic manipulation of gut microbiota as a novel treatment option for mental health are described, and important knowledge gaps are identified and discussed.     

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.     

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.     

Bidirectional Brain‐gut‐microbiota Axis in increased intestinal permeability induced by central nervous system injury

Central nervous system injuries may lead to the disorders of the hypothalamic‐pituitary‐adrenal axis, autonomic nervous system, and enteric nervous system. These effects then cause the changes in the intestinal microenvironment, such as a disordered intestinal immune system as well as alterations of intestinal bacteria. Ultimately, this leads to an increase in intestinal permeability. Inflammatory factors produced by the interactions between intestinal neurons and immune cells as well as the secretions and metabolites of intestinal flora can then migrate through the intestinal barrier, which will aggravate any peripheral inflammation and the central nervous system injury. The brain‐gut‐microbiota axis is a complex system that plays a crucial role in the occurrence and development of central nervous system diseases. It may also increase the consequences of preventative treatment. In this context, here we have summarized the factors that can lead to the increased intestinal permeability and some of the possible outcomes.     

Cerebrospinal fluid somatostatin and psychiatric illness

Somatostatin is a tetradecapeptide that is assuming increasing importance as a regulator of central nervous system activity. Originally identified as the hypothalamic growth hormone release-inhibiting factor, somatostatin has subsequently been shown to be extensively and selectively distributed throughout the central nervous system, to alter neuron excitability, to regulate and be regulated by the activity of classical neurotransmitters and neuropeptides, to exert a number of direct behavioral actions, and to display neuropsychiatric disorder-related alterations. In this article, a three-part study of cerebral spinal fluid (CSF) somatostatin in affective illness and schizophrenia is presented. In part 1, significant reductions in CSF somatostatin were observed in 49 bipolar and unipolar depressed patients relative to 47 controls. Values during depression were also significantly lower than those observed in affective disorder during the improved state or in schizophrenia. Diurnal studies involving paired AM and PM lumbar punctures revealed that depressed patients and normal volunteers had similar somatostatin values in the evening, despite having significantly different values in the morning. In part 2, the effects of several psychopharmacological agents on CSF somatostatin were examined, particularly the tricyclic anticonvulsant carbamazepine. A significant reduction of CSF somatostatin during treatment with carbamazepine was observed. The effect of carbamazepine on somatostatin could be related to its anticonvulsant, analgesic, or psychotropic effects. Part 3 deals with somatostatin as a major regulator of hypothalamic-pituitary-adrenal (HPA) axis activity. Somatostatin affects HPA activity by inhibiting, at a number of cellular levels, the stimulated release of adrenocorticotrophic hormone (ACTH) from the pituitary. A significant negative relationship between CSF somatostatin and the postdexamethasone plasma cortisol level in 22 depressed and 16 schizophrenic patients was observed. This relationship between low CSF somatostatin and escape from dexamethasone suppression was observed irrespective of diagnosis (i.e., depression or schizophrenia). Thus, there is indirect supporting evidence for a role for somatostatin dysregulation in the most consistently observed biological abnormality in depression, escape from dexamethasone suppression. Further study of somatostatin in neuropsychiatric disorders, and particularly depressive illness, offers great promise for better understanding their underlying affective, vegetative, cognitive, and physiological dysregulations.     

Autism-associated synaptic mutations impact the gut-brain axis in mice

Interactions between the gut microbiome and the brain affect mood and behaviour in health and disease. Using preclinical animal models, recent discoveries begin to explain how bacteria in the gut influence our mood as well as highlighting new findings relevant to autism. Autism-associated gene mutations known to alter synapse function in the CNS also affect inflammatory response and modify the enteric nervous system resulting in abnormal gastrointestinal motility and structure. Strikingly, these mutations additionally affect the gut microbiome in mice. This review describes the changes in gut physiology and microbiota in mouse models of autism with modified synapse function. The rationale for different regions of the gastrointestinal tract having variable susceptibility to dysfunction is also discussed. To dissect underlying biological mechanisms involving gut-brain axis dysfunction in preclinical models, a range of multidisciplinary approaches are required. This research will provide insights into the role of the gut-brain axis in health and neurodevelopmental disorders including autism.     

Combined oral contraceptives and mental health: Are adolescence and the gut-brain axis the missing links?

Combined oral contraceptives (containing synthetic forms of estradiol and progestins) are one of the most commonly used drugs among females. However, their effects on the gut-brain axis have not been investigated to a great extent despite clear evidence that suggest bi-directional interactions between the gut microbiome and endogenous sex hormones. Moreover, oral contraceptives are prescribed during adolescence, a critical period of development during which several brain structures and systems, such as hypothalamic-pituitary–gonadal axis, undergo maturation. Considering that oral contraceptives could impact the developing adolescent brain and that these effects may be mediated by the gut-brain axis, further research investigating the effects of oral contraceptives on the gut-brain axis is imperative. This article briefly reviews evidence from animal and human studies on the effects of combined oral contraceptives on the brain and the gut microbiota particularly during adolescence.     

Cytokines in schizophrenia and the effects of antipsychotic drugs

Growing evidence suggests that the immune, endocrine, and nervous systems interact with each other through cytokines, hormones, and neurotransmitters. The activation of the cytokine systems may be involved in the neuropathological changes occurring in the central nervous system (CNS) of schizophrenic patients. Numerous studies report that treatment with antipsychotic drugs affects the cytokine network. Hence, it is plausible that the influence of antipsychotics on the cytokine systems may be responsible for their clinical efficacy in schizophrenia. This article reviews current data on the cytokine-modulating potential of antipsychotic drugs. First, basic information on the cytokine networks with special reference to their role in the CNS as well as an up-to-date knowledge of the cytokine alterations in schizophrenia is outlined. Second, the hitherto published studies on the influence of antipsychotics on the cytokine system are reviewed. Third, the possible mechanisms underlying antipsychotics' potential to influence the cytokine networks and the most relevant aspects of this activity are discussed. Finally, limitations of the presented studies and prospects of future research are delineated.     

创伤后应激障碍的中枢神经系统机制

创伤后应激障碍（PTSD）所表现的各种精神症状，是与中枢神经系统（CNS）对应激信息的记忆密切相关的，本文就创伤后CNS的突触可塑性、CNS内神经递质的变化、PTSD的神经解剖学基础及改变、丘脑-垂体-肾上腺轴功能和PTSD治疗等方面对PTSD发生的中枢神经机制进行阐述。