从肠道菌群角度认识阿尔茨海默病的潜在发病机制

过去10年中,人们逐渐认识到肠道微生物群的多样性及菌群平衡在维护宿主健康中发挥的作用。肠道微生物及其代谢产物通过一系列的生化、免疫和生理功能环节与宿主进行交流,从而影响宿主的稳态和健康。阿尔茨海默病(Alzheimer’s disease,AD)是一种复杂的神经退行性疾病,其易感性和发展过程受年龄、遗传和表观遗传等因素的影响。研究发现,肠道微生物群的紊乱(组成改变和易位)与神经系统疾病(AD)有关,胃肠道通过肠脑轴与中枢神经系统进行沟通,包括对神经的直接作用、内分泌途径和免疫调控方式。动物模型、粪便菌群移植及益生菌干预为肠道菌群与AD的相关性提供了证据。外漏的细菌代谢产物可能直接损害神经元功能,也可能诱发神经炎症,促进AD的发病。本文主要综述了肠道微生物群与AD的关联和作用机制,以期为通过改善肠道菌群结构预防AD的可能干预措施提供依据。     

肠道菌群对代谢相关性脂肪肝的影响及运动干预研究进展

大量研究表明,肠道菌群与神经退行性疾病和代谢性疾病等多种疾病的发生和发展息息相关,菌群的种类和数量会受到遗传、饮食习惯、运动等因素的影响。在代谢相关脂肪性肝病中,肠道菌群的部分代谢物通过增加肝脏脂肪变性、改变肠道黏膜通透性等方式对疾病的发展起到促进作用,菌群的种类和数量变化与病情进展的关系也被广泛研究,但是两者发生的先后顺序仍不十分明确。运动可以增加肠道有益菌群的种类和数量,同时改善高脂饮食导致的肠道菌群紊乱,并有效缓解代谢相关脂肪性肝病的病情,肠道菌群也能对机体的运动能力产生影响,但运动是如何通过肠道菌群来改善代谢相关脂肪性肝病的机制尚不十分明确。本文通过综述三者的相互关系来阐述肠道菌群和运动在代谢相关脂肪性肝病中发挥的重要作用。     

肠道菌群-阿尔茨海默病防治的新靶标

阿尔茨海默病(Alzheimer's disease,AD)是一种渐进性中枢神经系统退行性疾病,其发病机制仍未完全阐明.近年来,随着菌群-肠-脑轴研究的兴起,肠道菌群在AD发生和发展中的作用日益得到重视.本文综述了AD患者的肠道菌群特征,肠道菌群影响AD的主要途径及益生菌、抗生素和饮食等对AD患者的干预作用,为制定靶向...     

运动调节肠道菌群改善机体代谢机制研究进展

研究发现,机体肠道内寄居着数以万亿的微生物,其代谢产物及其对肠道健康的影响效应对多种慢病的发生发展具有重要的调节作用。最新研究认为肠道菌群可被视为一种重要的内分泌器官,通过探究肠道菌群的变化对机体代谢稳态和生理状态的影响,可更好地了解肠道菌群的功能及其对健康调节的重要机制。有证据表明,人类肠道菌群可受内、外环境等多种因素的影响,其中最主要的两大影响因素为饮食和运动。目前,饮食与肠道菌群的关系研究已较为广泛,而运动对机体肠道菌群的影响仍有很多尚待解决的问题。本文针对运动对肠道菌群的调节及其对机体健康影响研究的最新进展进行综述,以期为今后探究运动调节肠道菌群、改善机体健康的机制提供理论依据。     

不同年龄肠道菌群的变化和阿尔茨海默病的关系

阿尔茨海默病(Alzheimer’s disease,AD)是一种以进行性认知障碍为临床表现的神经退行性疾病,具体发病机制尚不明确。肠道菌群失调与AD的发生密切相关,在AD的发生发展中发挥重要作用。肠道菌群可以通过神经、内分泌和免疫等通道与中枢神经系统进行交流,并且可能通过产生有害物质、分泌或调节神经递质以及诱导神经炎症等方式引起神经退行性病变。本文通过总结肠道菌群在各年龄段与认知的关系,分析肠道菌群影响AD的可能机制,以期为AD的防治提供新的研究方向。     

运动调控肠道菌群防治肌少症的作用与机制

肌少症是一种与年龄相关的骨骼肌质量、力量和功能丧失的衰老性综合征。肠道菌群及其代谢物在肌少症的发生发展中扮演重要角色，肠道菌群失调会导致骨骼肌炎性细胞因子表达上调、胰岛素抵抗、线粒体功能障碍及加速肌细胞凋亡进而加快肌肉衰老。研究表明，运动能作为有效改善肠道菌群的非药物干预手段，会影响肠道微生物区系多样性(例如提高颤螺菌属和环状螺旋菌属的表达以及增加肠道菌群α、β多样性的相对丰度等),改善肠道菌群稳态。新近研究表明，运动能通过调节肠道菌群抑制炎症反应、维持肌肉蛋白质合成代谢、改善线粒体功能障碍和改善胰岛素敏感性等途径在肌少症的防治中发挥有益效应。该文详细阐述了肠道菌群对肌少症中的诊疗作用及其机制，并围绕不同运动形式对肠道菌群的影响，以及以肠道菌群为靶点进行运动干预防治肌少症的生物学机制进行深入探讨，旨在为肌少症疾病的防治提供科学依据。     

从代谢产物论述肠道菌群与阿尔茨海默病

阿尔茨海默病(Alzheimer′sDisease, AD)是最常见的一种痴呆类型,其主要表现为记忆、语言和认知能力的逐渐丧失。肠道菌群(Gut Microbiota,GM)作为近年来的探讨热点,引起学者们的广泛关注。有研究证明肠道菌群与阿尔茨海默病密切相关,其可通过代谢产物等多种方式来参与AD的发生与发展,从代谢产物三甲胺N-氧化物、γ-氨基丁酸、乙酰胆碱、β-甲基氨基-L-丙氨酸等来论述肠道菌群与阿尔茨海默病的关系。     

基于调节肠道菌群的功能性低聚糖改善肥胖的研究进展

肥胖是机体脂肪积聚过多的一种典型的能量过剩疾病,是导致2型糖尿病和心血管疾病等一系列代谢性疾病的主要原因之一,已成为威胁全球健康的重大公共卫生问题。肠道菌群作为机体能量代谢调控的重要参与者,在肥胖及相关代谢性疾病的发生发展中起着关键作用,通过饮食干预调节肠道菌群,进而改善机体健康状况将是未来的研究热点之一。已有研究表明,功能性低聚糖作为一类典型的新型益生元,可调节肠道菌群结构及其代谢产物的水平,影响机体能量代谢过程,改善肥胖及相关代谢性疾病。本文主要对肠道菌群在肥胖中的潜在作用机制,以及常见功能性低聚糖调节肠道菌群改善肥胖的作用效果进行综述,以期为通过靶向肠道菌群精准干预肥胖及相关代谢性疾病提供一些新的潜在防治策略。

     

肠道菌群与中枢神经系统相互作用及相关疾病

肠道菌群参与宿主的多项生理过程,包括营养物质吸收、代谢及免疫系统的发育成熟、抵抗外来病原体入侵等,新的研究显示肠道菌群通过神经、内分泌、代谢和免疫的途径参与了肠道和中枢神经系统的双向调节。肠道菌群的变化与自闭症、多发性硬化、帕金森病、焦虑和抑郁症等一系列神经精神疾病有关,通过改善肠道菌群的微生态疗法有望成为治疗和预防一些神经系统疾病的有效措施。     

运动干预肠道菌群对代谢性疾病的改善及其机制

肠道菌群动态平衡状态是宿主身体健康的前提,因胃肠道菌群失衡而引发的内源性低度、慢性、系统性炎症反应才是触发代谢性疾病的根本诱因。运动作为一种非药物性治疗处方,无论是在老鼠模型还是人体实验中都能够安全有效的提高肠道菌群丰富度,改善肠道菌群结构,并在减缓代谢紊乱以及抵抗炎症因子中发挥积极作用。在本文中,综述最近关于运动作为环境应激因素对肠道菌群结构和多样性变化的影响,以及这些变化如何发挥预防疾病促进健康的积极作用。     

The role of gut microbiota in pathogenesis of Alzheimer's disease

This paper describes the effects of the gut microbiota on the pathogenesis of Alzheimer's pathology by evaluating the current original key findings and identifying gaps in the knowledge required for validation. The diversity of the gut microbiota declines in the elderly and in patients with Alzheimer's disease (AD). Restoring the diversity with probiotic treatment alleviates the psychiatric and histopathological findings. This presents a problem: How does gut microbiota interact with the pathogenesis of AD? The starting point of this comprehensive review is addressing the role of bacterial metabolites and neurotransmitters in the brain under various conditions, ranging from a healthy state to ageing and disease. In the light of current literature, we describe three different linkages between the present gut microbiome hypothesis and the other major theories for the pathogenesis of AD as follows: bacterial metabolites and amyloids can trigger central nervous system inflammation and cerebrovascular degeneration; impaired gut microbiome flora inhibits the autophagy-mediated protein clearance process; and gut microbiomes can change the neurotransmitter levels in the brain through the vagal afferent fibres.     

肠道微生物调控宿主食欲的研究进展

肠道微生物与宿主代谢相互作用,可调节机体的生理功能。宿主机体中存在"微生物-肠道-大脑轴",肠道菌群可通过多种途径影响中枢神经系统,进而对宿主摄食等行为产生影响。食物中不易被宿主消化吸收的膳食纤维等营养物质,被肠道微生物发酵可产生多种代谢产物,这些代谢产物作为信号分子可通过不同途径介导中枢神经系统,进而调控宿主食欲。本文主要综述了肠道微生物及其代谢产物对中枢神经系统与宿主食欲的影响及其可能的调控途径与机制,以加深肠道微生物在调控宿主食欲方面的新认识。     

肠道菌群与脊髓损伤并发症

脊髓损伤是严重的致残性神经系统疾病,脊髓损伤后产生的水肿、炎症反应和代谢紊乱等并发症是致使脊髓损伤继发性加重的主要原因。近年来,随着对肠道微生物的研究越来越深入,肠道菌群对神经系统疾病的影响得到广泛关注。肠道菌群可以通过调节机体能量代谢、炎症反应及作用于神经内分泌和脑-肠轴的途径影响中枢神经系统疾病。最近研究发现,肠道菌群与脊髓损伤并发症的关系非常紧密。脊髓损伤后肠道菌群的变化可能影响脊髓损伤后并发症发生以及加重。本文主要就肠道菌群对脊髓损伤后并发症的影响和可能的作用机制进行综述,为临床研究和治疗脊髓损伤提供新思路。     

Mind-altering with the gut: Modulation of the gut-brain axis with probiotics

It is increasingly evident that bidirectional interactions exist among the gastrointestinal tract, the enteric nervous system, and the central nervous system. Recent preclinical and clinical trials have shown that gut microbiota plays an important role in these gut-brain interactions. Furthermore, alterations in gut microbiota composition may be associated with pathogenesis of various neurological disorders, including stress, autism, depression, Parkinson’s disease, and Alzheimer’s disease. Therefore, the concepts of the microbiota-gut-brain axis is emerging. Here, we review the role of gut microbiota in bidirectional interactions between the gut and the brain, including neural, immune-mediated, and metabolic mechanisms. We highlight recent advances in the understanding of probiotic modulation of neurological and neuropsychiatric disorders via the gut-brain axis.     

Functional effects of gut microbiota-derived metabolites in Alzheimer's disease

The precise causation of Alzheimer's disease (AD) is unknown, and the factors that contribute to its etiology are highly complicated. Numerous research has been conducted to investigate the potential impact of various factors to the risk of AD development or prevention against it. A growing body of evidence suggests to the importance of the gut microbiota-brain axis in the modulation of AD, which is characterized by altered gut microbiota composition. These changes can alter the production of microbial-derived metabolites, which may play a detrimental role in disease progression by being involved in cognitive decline, neurodegeneration, neuroinflammation, and accumulation of Aβ and tau. The focus of this review is on the relationship between the key metabolic products of the gut microbiota and AD pathogenesis in the brain. Understanding the action of microbial metabolites can open up new avenues for the development of AD treatment targets.     

帕金森症与肠道微生物

帕金森症是一种多发于中老年期的、慢性的、进行性的、可致残的神经系统退行性疾病。近年来许多研究发现帕金森症患者的胃肠道症状往往早于运动症状数年出现并在早期帕金森症患者的肠神经系统内发现病理组织学改变,提示肠道可能是帕金森病理早期发生的位置。肠道微生物作为与人体共生的最大微生物群落,不仅影响宿主的营养吸收和能量代谢,促进免疫系统发育和调节肠黏膜免疫系统,促进和抑制炎症反应,还可以通过肠—脑轴影响中枢神经系统,还可能是导致神经系统退行性病变发生的原因之一。目前已有研究发现帕金森症患者的肠道微生物与健康对照之间差异有统计学意义,提示从改善肠道微生物的角度入手,通过益生菌干预来恢复肠道微生态的平衡可能成为治疗帕金森症的一种新方法。     

肠道菌群与精神分裂症的研究进展

精神分裂症是一种精神障碍疾病。除了遗传因素外,一些环境因素也参与了精神分裂症的发生,肠道微生物群是近年来发现的主要影响因素之一。研究表明,精神分裂症患者肠道菌群普遍发生了紊乱,肠道菌群通过肠-脑轴影响神经功能和疾病。肠道菌群可以通过影响神经系统发育、免疫和代谢功能来诱导精神分裂症的发生,肠道菌群可能是精神分裂症防治的有效靶点,调节肠道菌群可能是防治精神分裂症的一种潜在方法。本文就精神分裂症的易感因素、肠道菌群在精神分裂症中的作用、机制以及防治策略等方面的研究进展进行综述。     

Nutritional modulation of the intestinal microbiota; future opportunities for the prevention and treatment of neuroimmune and neuroinflammatory disease

The gut–brain axis refers to the bidirectional communication between the enteric nervous system and the central nervous system. Mounting evidence supports the premise that the intestinal microbiota plays a pivotal role in its function and has led to the more common and perhaps more accurate term gut–microbiota–brain axis. Numerous studies have identified associations between an altered microbiome and neuroimmune and neuroinflammatory diseases. In most cases, it is unknown if these associations are cause or effect; notwithstanding, maintaining or restoring homeostasis of the microbiota may represent future opportunities when treating or preventing these diseases. In recent years, several studies have identified the diet as a primary contributing factor in shaping the composition of the gut microbiota and, in turn, the mucosal and systemic immune systems. In this review, we will discuss the potential opportunities and challenges with respect to modifying and shaping the microbiota through diet and nutrition in order to treat or prevent neuroimmune and neuroinflammatory disease.     

Neuropathy in COVID-19 associated with dysbiosis-related inflammation

Although COVID-19 affects mainly lungs with a hyperactive and imbalanced immune response, gastrointestinal and neurological symptoms such as diarrhea and neuropathic pains have been described as well in patients with COVID-19. Studies indicate that gut–lung axis maintains host homeostasis and disease development with the association of immune system, and gut microbiota is involved in the COVID-19 severity in patients with extrapulmonary conditions. Gut microbiota dysbiosis impairs the gut permeability resulting in translocation of gut microbes and their metabolites into the circulatory system and induce systemic inflammation which, in turn, can affect distal organs such as the brain. Moreover, gut microbiota maintains the availability of tryptophan for kynurenine pathway, which is important for both central nervous and gastrointestinal system in regulating inflammation. SARS-CoV-2 infection disturbs the gut microbiota and leads to immune dysfunction with generalized inflammation. It has been known that cytokines and microbial products crossing the blood-brain barrier induce the neuroinflammation, which contributes to the pathophysiology of neurodegenerative diseases including neuropathies. Therefore, we believe that both gut–lung and gut–brain axes are involved in COVID-19 severity and extrapulmonary complications. Furthermore, gut microbial dysbiosis could be the reason of the neurologic complications seen in severe COVID-19 patients with the association of dysbiosis-related neuroinflammation. This review will provide valuable insights into the role of gut microbiota dysbiosis and dysbiosis-related inflammation on the neuropathy in COVID-19 patients and the disease severity.