过敏性疾病中肠道菌群对肠黏膜免疫细胞的调节作用

胃肠道是机体与外源性抗原的主要接触部位。其在对食物抗原及肠道菌群产生免疫耐受的同时还能有效抵御外来病原体的入侵。一旦肠道的耐受不能建立就会导致疾病的发生,这时不仅仅会引起局部的炎症反应同,亦导致全身的过敏性炎症反应。早期的“卫生假说”提出,过敏性疾病发生率的增加与环境的改变相关,而其中最主要的是肠道菌群的改变。对照研究和前瞻性调查研究也支持了肠道菌群的改变与过敏性疾病的发生具有相关性的观点。有研究提出,双歧杆菌、乳酸杆菌等益生菌的应用不仅可以缓解由于过敏所致的炎症反应、降低特异性IgE的产生等,益生菌的…     

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。     

运动调控肠道菌群防治神经退行性疾病的研究进展

随着人口老龄化的发展,神经退行性疾病逐渐成为我国公共卫生领域的重大问题。肠道菌群的组成和丰度的改变与神经退行性疾病的发生发展密切相关,而体育锻炼被认为是肠道菌群的重要调节因素,并且不同的体育运动对肠道菌群的多样性和菌群结构均有较好的调控作用,因此运动、肠道微生物群和神经退行性疾病三者之间的动态相互作用也成为研究热点。多项研究结果均证实,运动可通过调控肠道菌群从而调节神经活性代谢物分泌、减少β淀粉样蛋白沉积、降低氧化应激水平和改善血脑屏障功能等,在神经退行性疾病防治方面发挥重要作用。本文以阿尔茨海默病、帕金森病和肌萎缩侧索硬化症三种神经退行性疾病为研究对象,主要阐述运动、肠道菌群和神经退行性疾病相关的研究进展,以期为运动预防神经退行性疾病提供新的思路和理论依据。     

肠道微生物菌群与帕金森症相关性的研究进展

众所周知,肠道菌群对机体功能具有重要调节作用,除对常见的消化功能调节外,还对中枢神经系统有诸多影响,即通过肠道菌群-肠-脑轴进行调节。帕金森症(Parkinson′s disease,PD)发病率仅次于阿尔茨海默病,是常见的神经退行性疾病,严重影响人们生活质量。其特征为黑质―多巴胺能神经元受损,是α-突触核蛋白代谢异常引起的疾病,多巴胺能神经元细胞内可见大量的α-突触核蛋白累积,主要影响运动系统,但也可出现消化不良等胃肠功能紊乱的症状。而α-突触核蛋白也同样存在于肠道,并以特殊的方式进入到神经系统,从而参与帕金森症的发病。     

肠道菌群与神经系统疾病

人类肠道菌群是数以万亿的细菌组成的高度多样化的生态系统,菌群失调与多个系统疾病有关联。肠道菌群通过菌群-肠-脑轴与神经系统多途径双向互作,能引起神经免疫炎症反应、肠黏膜和血脑屏障功能改变、直接刺激迷走神经和肠道神经系统脊神经、神经内分泌-下丘脑-垂体-肾上腺轴,造成神经系统疾病。肠道菌群的代谢产物也有一定的作用。文中综述自闭症谱系障碍、多发性硬化、帕金森病、癫痫、吉兰巴雷综合征、阿尔茨海默病、视神经脊髓炎、肝性脑病、肌萎缩侧索硬化、精神分裂症、抑郁症、慢性疲劳综合征、亨廷顿病、脑卒中等肠道菌群改变特征及其干预措施的研究进展。目前肠道菌群的研究还处在初级阶段,因果关系和机制方面的研究比较少,这对精准实施菌群临床干预措施具有重要意义,期待将来有所突破成为一些神经系统疾病治疗的新路径。     

常乐康对乙肝肝硬化患者肠道菌群和肠道黏膜屏障功能的影响

目的探讨常乐康对乙肝肝硬化患者肠道菌群及肠道黏膜屏障功能的影响。方法收集乙肝肝硬化代偿期患者87例,其中治疗组48例,对照组39例。所有患者给予相同的常规护肝对症治疗,其中治疗组加用常乐康治疗8周。治疗结束后观察患者肠道菌群、肠道黏膜屏障功能和系统性炎症反应的改善情况。结果常乐康治疗后,患者肠道菌群中梭菌属I簇和XI簇及双歧杆菌属细菌数量显著升高,而肠杆菌科细菌及肠球菌属细菌数量显著降低;患者血清D-乳酸,内毒素(LPS)和二胺氧化酶(DAO)的水平显著下降,血清中促炎因子TNF-α和IFN-γ水平显著下降,而抗炎因子IL-10水平显著上升。结论常乐康可显著改善乙肝肝硬化患者肠道菌群组成和肠道黏膜屏障功能,有效减轻系统性炎症反应,可作为阻止乙肝肝硬化病情进展的有效辅助治疗方法。     

肠道菌群与糖尿病的研究进展

近年来的研究表明,糖尿病的病因除了肥胖、遗传、胰岛素自身功能不全外,还可能与肠道菌群密切相关。目前认为,肠道菌群的结构性失衡是糖尿病发生的一种可能的重要机制。具体表现为菌群多样性和稳定性遭到破坏,如有益菌菌群的减少亦或条件致病菌菌群的增强,可以诱发肠道产生低度慢性炎症,促使细菌内毒素释放,从而导致胰岛素抵抗。籍此进一步影响机体对糖和能量的吸收,同时促进脂肪的合成与存储,即糖尿病病变发生。与此,饮食干预疗法和益生菌的摄入治疗,尤其是后者,可明显改善病情。其可能的机制在于调节肠道屏障功能、通透性以及肠黏膜免疫功能。     

肠道菌群和肠黏膜屏障在类风湿关节炎中的作用CSCD

类风湿关节炎（rheumatoid arthritis,RA）是一种自身免疫性疾病,致畸率与致残率较高,发病机制尚不清楚,目前尚未有特效药可完全治愈。近年来,国内外相关研究表明RA的发病机制与肠道菌群和肠黏膜屏障密切相关。积极调节肠道菌群和改善肠黏膜屏障可有效缓解RA的关节炎症状,这可能作为RA干预的新靶点。肠道菌群失调引起肠道微生态失衡,一系列有害物质侵入并诱发肠道炎症反应,导致肠道黏膜屏障功能障碍,可能参与RA的发病,但具体作用机制还需进一步明确。本文对肠道菌群和肠黏膜屏障在RA中的具体作用及影响进行总结归纳,以期为治疗RA提供新方向。     

肠道菌群影响黏膜屏障结构与功能的研究进展

肠道黏膜屏障具有防止致病性抗原侵入、维护肠道健康的功能。而肠道菌群是肠道黏膜屏障的重要构成部分,肠道菌群失调会导致肠道黏膜屏障的损伤,引起炎性肠病、肠易激综合征及肝、肾等多种疾病的发生发展。因此,本文从肠道黏膜的结构与功能及肠道菌群对其的影响等方面归纳总结肠道菌群对屏障系统的调控作用,从调节肠道微生态平衡、促进黏液分泌、影响紧密连接和肠道上皮通透性、激发肠黏膜免疫、调控肠上皮凋亡、影响肠上皮DNA稳定性及产生特殊代谢产物等方面阐述其作用机制,为临床胃肠道疾病及其并发症的治疗提供新的思路和方法。     

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。     

肠黏膜屏障与肠道菌群的相互关系

摘要：人类肠道中微生物群与肠道环境相互作用以维持机体健康。肠黏膜屏障主要由黏液层、肠道菌群、肠道免疫系统和肠上皮细胞本身的完整性等构成。肠道作为直接与大量菌群接触的器官,其屏障功能在肠道健康中的作用尤为显著。肠道菌群与肠道屏障相互作用,保持肠道菌群与肠道屏障相对稳定,肠道菌群参与肠道免疫反应的建立,共同建立机体天然防御系统,在保持肠道免疫的动态平衡中具有重要作用。当两者之间的平衡被打破时,可诱发功能性胃肠病（如肠易激综合征）及免疫相关性疾病（如炎症性肠病）。本文主要阐述肠黏膜屏障与肠道菌群之间的相互关系以及与肠道屏障功能障碍相关的肠道疾病。     

肠道菌群与阿尔茨海默病的研究进展

阿尔茨海默病(Alzheimer′s disease,AD)是一种神经退行性疾病,呈进行性发展趋势,严重影响患者的生活质量,给社会和家庭带来了沉重的经济负担。随着人口老龄化进程的不断加剧,AD患者数量不断增加,而其发病原因、发病机制仍不明确,缺乏有效的防治方法。近年来,研究表明肠道菌群通过多种途径参与AD的发生发展,调整肠道菌群有望成为预防和治疗AD的有效措施之一,其可能的作用机制包括减轻AD的病理改变、改善脑内炎症、影响血脑屏障及神经递质的产生。     

肠道菌群与抑郁症相关性的研究进展

正常人体内的肠道菌群数量可达100万亿,可参与人体的多项生理活动,包括营养物质的吸收与代谢、免疫系统的发育与成熟、抵挡外来病原体的入侵等,对人类的健康有着至关重要的作用。近年来发现肠道中的定植微生物与抑郁症、自闭症、焦虑症和帕金森病等一系列的神经精神疾病密切相关。最新研究表明,肠道菌群是通过神经、体液、代谢和免疫多种途径双向调节肠道和中枢神经系统的。目前,随着医学技术和医学理论的的提高,抑郁症与肠道菌群间的关系受到极大地重视。本文从肠道菌群对抑郁症的影响机制以及益生菌对抑郁症的改善作用两方面来综述肠道菌群与抑郁症相关性的最新进展。     

抗生素所致腹泻大鼠肠屏障功能损伤及乳酸杆菌保护机制的研究

目的探讨抗生素对所致腹泻大鼠肠道屏障功能、肠道菌群结构和肠道细菌移位的影响及乳酸杆菌制剂的保护机制。方法采用细菌培养法动态测定抗生素所致腹泻大鼠肠道菌群变化及肠系膜淋巴结、肝脏、脾脏和结肠组织的移位细菌量;应用光镜和电子显微镜观察肠黏膜组织超微结构变化。结果应用抗生素可致大鼠腹泻,肠道菌群失调,肠黏膜组织受损,发生肠道细菌移位。大肠埃希菌攻击可加重肠道菌群失调和肠黏膜损伤程度,促发细菌移位发生。乳酸杆菌可扶正肠菌群结构,修复损伤的肠黏膜,抑制肠细菌移位发生。结论阐明了抗生素、肠黏膜屏障功能、肠道菌群结构和肠道细菌移位间的互为因果,相互影响的关系。微生态制剂在维持机体微生态平衡、修复肠黏膜方面具有保护作用。     

Research progress on the regulation mechanism of probiotics on the microecological flora of infected intestines in livestock and poultry

The animal intestine is a complex ecosystem composed of host cells, gut microbiota and available nutrients. Gut microbiota can prevent the occurrence of intestinal diseases in animals by regulating the homeostasis of the intestinal environment. The intestinal microbiota is a complex and stable microbial community, and the homeostasis of the intestinal environment is closely related to the invasion of intestinal pathogens, which plays an important role in protecting the host from pathogen infections. Probiotics are strains of microorganisms that are beneficial to health, and their potential has recently led to a significant increase in studies on the regulation of intestinal flora. Various potential mechanisms of action have been proposed on probiotics, especially mediating the regulation mechanism of the intestinal flora on the host, mainly including competitive inhibition of pathogens, stimulation of the host's adaptive immune system and regulation of the intestinal flora. The advent of high-throughput sequencing technology has given us a clearer understanding and has facilitated the development of research methods to investigate the intestinal microecological flora. This review will focus on the regulation of probiotics on the microbial flora of intestinal infections in livestock and poultry and will depict future research directions.     

儿童重症手足口病肠道菌群和肠道黏膜通透性的研究进展

手足口病是由肠道病毒引起的儿童常见的传染病,有研究显示肠道病毒进人消化道后在肠黏膜内复制繁殖并持续释放到血液而发病,肠道黏膜是病毒人侵和增殖的主要场所。肠道菌群能防御感染和增强肠道屏障功能,肠道屏障功能在防御外源性和内源性感染方面发挥重要作用,同时在维持肠道免疫稳定和平衡方面也有重要的作用。益生菌是指数量适当时对宿主健康有利的活微生物,有研究报道益生菌在辅助治疗手足口病上是有效的。开展这方面的研究,对于探索手足口病的发病机制和益生菌防治手足口病有十分重要的意义。     

TLR signaling in the gut in health and disease

The human intestine has evolved in the presence of diverse enteric microflora. TLRs convert the recognition of pathogen-associated molecules in the gut into signals for anti-microbial peptide expression, barrier fortification, and proliferation of epithelial cells. Healing of injured intestinal epithelium and clearance of intramucosal bacteria require the presence of intact TLR signaling. Nucleotide oligomerization domain (Nod)1 and Nod2 are additional pattern recognition receptors that are required for defense against invasive enteric pathogens. Through spatial and functional localization of TLR and Nod molecules, the normal gut maintains a state of controlled inflammation. By contrast, patients with inflammatory bowel disease demonstrate inflammation in response to the normal flora. A subset of these patients carry polymorphisms in TLR and CARD15/NOD2 genes. A better understanding of the delicate regulation of TLR and Nod molecules in the gut may lead to improved treatment for enteric infections and idiopathic inflammatory bowel diseases.     

The protective roles of NLRP6 in intestinal epithelial cells

The evolution of chronic inflammatory diseases is thought to be due to a combination of host genetic variations and environmental factors that include the alteration of intestinal flora, termed “dysbiosis.” The intestinal mucosal barrier includes a chemical barrier and physical barrier that have important roles in protecting the intestine against inflammatory injury. The chemical barrier includes antimicrobial peptides (AMPs), and the physical barrier includes a mucous layer, a monolayer of intestinal epithelial cells and cell junctions. The intestinal mucosal barrier is not a static barrier, but rather, it strongly interacts with the gut microbiome and cells of the immune system. Correct expression of AMPs, together with mucus and balanced epithelial cell proliferation, prevents the occurrence of disease. NLRP6, a member of the nucleotide‐binding domain, leucine‐rich repeat‐containing (NLR) innate immune receptor family, participates in the progression of intestinal inflammation and enteric pathogen infections. It has become apparent in recent years that NLRP6 is important in disease pathogenesis, as it responds to internal ligands that lead to the release of AMPs and mucus, thus regulating the regeneration of intestinal epithelial cells. This review summarizes the activation of NLRP6 and its protective role in the intestinal epithelial cell.     

Intestinal Pathology and Gut Microbiota Alterations in a Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Mouse Model of Parkinson’s Disease

Patients with Parkinson’s disease (PD) often have non-motor symptoms related to gastrointestinal (GI) dysfunction, such as constipation and delayed gastric emptying, which manifest prior to the motor symptoms of PD. Increasing evidence indicates that changes in the composition of the gut microbiota may be related to the pathogenesis of PD. However, it is unclear how GI dysfunction occurs and how gut microbial dysbiosis is caused. We investigated whether a neurotoxin model of PD induced by chronic low doses of MPTP is capable of reproducing the clinical intestinal pathology of PD, as well as whether gut microbial dysbiosis accompanies this pathology. C57BL/6 male mice were administered 18 mg/kg MPTP twice per week for 5 weeks via intraperitoneal injection. GI function was assessed by measuring the 1-h stool frequency and fecal water content; motor function was assessed by pole tests; and tyrosine hydroxylase and alpha-synuclein expression were analyzed. Furthermore, the inflammation, intestinal barrier and composition of the gut microbiota were measured. We found that MPTP caused GI dysfunction and intestinal pathology prior to motor dysfunction. The composition of the gut microbiota was changed; in particular, the change in the abundance of Lachnospiraceae, Erysipelotrichaceae, Prevotellaceae, Clostridiales, Erysipelotrichales and Proteobacteria was significant. These results indicate that a chronic low-dose MPTP model can be used to evaluate the progression of intestinal pathology and gut microbiota dysbiosis in the early stage of PD, which may provide new insights into the pathogenesis of PD.