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。     

肠道菌群与肠黏膜免疫

肠道不仅是吸收、消化和营养物质交换的重要场所 ,也是人体最大的免疫器官。人的肠黏膜面积巨大 ,约 2倍于皮肤的表面 ,每时每刻黏膜都要接触大量抗原 ,担负着重要的免疫功能。越来越多的证据表明肠黏膜免疫功能与寄居在肠道中为数众多的肠道菌群 (intestinalflora)有密切关系。本文就该领域的研究作一综述。1　肠道菌群的变迁与肠黏膜屏障人出生时肠道是无菌的 ,肠道菌群定植开始于出生后。菌群的发展和肠黏膜屏障的建立是一个渐进而互动的过程。母亲的肠菌群是新生儿肠道定植细菌的重要来源。定植也取决于环境因素。最初 ,任何厌氧菌都可…     

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。     

多糖对肠道功能调节作用的研究进展

肠道是机体重要的消化器官,亦是共生微生物群的主要寄居场所,在维持机体正常生命活动如免疫和内分泌功能中发挥着重要作用。 肠道功能紊乱与疾病的发生以及发展过程密切相关。近年来,多项研究结果显示,多糖具有肠道功能调节作用,包括通过作用于肠道黏膜 参与机体免疫过程、保护肠道屏障结构和功能的完整性、调节肠道菌群组成以及刺激肠道内分泌。从伴随疾病过程中的肠道功能紊乱的角度, 对多糖调节肠道功能的作用机制进行综述。     

肠上皮与肠道微生物相互作用研究进展

肠道不仅是消化和吸收的主要场所,也是机体重要的免疫器官。人类肠道中存在着超过百万亿的微生物,其在漫长的自然选择及共同进化中与宿主形成了紧密的共生关系。肠上皮是先天免疫的一个组成部分,通过各种黏膜保护屏障将肠腔内容物与机体内环境分隔开。各种肠上皮细胞相互协调维持肠道内稳态,并与肠道微生物、肠黏膜免疫系统共同形成抵御肠腔内有害抗原的第一道防线。肠上皮作为肠道微生物和肠黏膜免疫系统相互作用的枢纽,在黏膜免疫防御体系中具有重要作用,本文就肠上皮与肠道微生物之间的相互作用进行综述,旨在深入理解肠上皮,为探索肠道相关疾病的治疗提供新思路。     

活血化瘀法对肠道菌群结构及 肠屏障功能影响的研究

随着人们对于肠道菌群种类以及作用认识的逐渐深入,我们发现作为人体庞大而又复杂的微生态系统,肠道菌群的结构及和菌群分布有紧密联系的肠屏障功能的改变与人体的健康息息相关。中药作为传统医学的一种治疗方法,其对人体的治疗作用是十分显著的,而活血化瘀法是使用具有消散作用及攻逐体内淤血作用的药物来治疗人类各种疾病的一种方法,这种方法对于肠道菌群以及肠屏障功能也产生了深远的影响。本文围绕肠道菌群结构改变及肠黏膜屏障功能的变化,对近十年关于肠道菌群与活血化瘀方药的相关文献进行综述,探究活血化瘀法(中药及中药复方)对于肠道菌群的影响,为临床治疗提供新思路。     

肠道菌群-肠-脑-肌轴信号交流的研究进展

肠道菌群及其代谢产物在老年神经退行性疾病、胃肠道疾病以及肌肉骨骼系统性疾病的发病与康复中的作用越来越受到关注。肠道菌群及其代谢产物可通过免疫、内分泌和神经系统等多种途径调节大脑神经或肌肉骨骼系统功能;反之,肠道、大脑或肌肉骨骼系统也可通过炎症、代谢或线粒体通路作用于肠道系统,调节肠道菌群微生态,形成肠道菌群与肠-脑、肠-肌、 肠-脑-肌之间的双向信号交流机制,从而影响机体健康。因此,本综述总结了肠道菌群如何通过代谢产物、肠道通透性和免疫-神经通路建立起肠-脑-肌之间的相互联系,为促进大脑神经的可塑性和改善肌肉健康提供新思路。     

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。     

肠道菌群与肠黏膜免疫及相关肠道疾病的研究进展

肠道菌群与肠黏膜免疫之间存在密切的关系,二者相互促进、相互影响,共同维持肠道微生态的平衡,二者失衡可造成肠道器质性及功能性的病变。对肠道菌群、肠黏膜免疫及相关肠道疾病的研究进展作一综述。     

肠道和呼吸道菌群与肺部疾病的研究新进展

宿主微生物群落对机体局部以及系统免疫的影响已逐渐引起人们的关注,目前发现局部的微生物群落能够对机体远端部位的免疫能力造成影响。肠道和呼吸道菌群稳态对机体免疫系统发育以及抗病原微生物感染至关重要,肠道和呼吸道菌群失衡与炎症性疾病、代谢性疾病以及过敏性疾病密切相关。肠道和呼吸道菌群失衡会通过"肠—肺轴"的相互作用,引起免疫系统改变与急性、慢性肺部疾病的发生。在这篇综述中,我们对肠道微生物和呼吸道微生物在肠-肺轴中发挥作用的研究进展作一总结,并对从微生物角度进行疾病治疗干预的可能性进行分析。     

A role for IL-22 in the relationship between intestinal helminths,gut microbiota and mucosal immunity

The intestinal tract is home to nematodes as well as commensal bacteria (microbiota), which have coevolved with the mammalian host. The mucosal immune system must balance between an appropriate response to dangerous pathogens and an inappropriate response to commensal microbiota that may breach the epithelial barrier, in order to maintain intestinal homeostasis. IL-22 has been shown to play a critical role in maintaining barrier homeostasis against intestinal pathogens and commensal bacteria. Here we review the advances in our understanding of the role of IL-22 in helminth infections, as well as in response to commensal and pathogenic bacteria of the intestinal tract. We then consider the relationship between intestinal helminths and gut microbiota and hypothesize that this relationship may explain how helminths may improve symptoms of inflammatory bowel diseases. We propose that by inducing an immune response that includes IL-22, intestinal helminths may enhance the mucosal barrier function of the intestinal epithelium. This may restore the mucosal microbiota populations from dysbiosis associated with colitis and improve intestinal homeostasis.     

Role of the enteric microbiota in intestinal homeostasis and inflammation

The mammalian intestine encounters many more microorganisms than any other tissue in the body thus making it the largest and most complex component of the immune system. Indeed, there are greater than 100 trillion (10¹⁴) microbes within the healthy human intestine, and the total number of genes derived from this diverse microbiome exceeds that of the entire human genome by at least 100-fold. Our coexistence with the gut microbiota represents a dynamic and mutually beneficial relationship that is thought to be a major determinant of health and disease. Because of the potential for intestinal microorganisms to induce local and/or systemic inflammation, the intestinal immune system has developed a number of immune mechanisms to protect the host from pathogenic infections while limiting the inflammatory tissue injury that accompanies these immune responses. Failure to properly regulate intestinal mucosal immunity is thought to be responsible for the inflammatory tissue injury observed in the inflammatory bowel diseases (IBD; Crohn disease, ulcerative colitis). An accumulating body of experimental and clinical evidence strongly suggests that IBD results from a dysregulated immune response to components of the normal gut flora in genetically susceptible individuals. The objective of this review is to present our current understanding of the role that enteric microbiota play in intestinal homeostasis and pathogenesis of chronic intestinal inflammation.     

Regulation of immune response at intestinal and peripheral sites by probiotics

The gut associated lymphoid tissue (GALT) should protect intestinal mucosa against pathogens, but also avoid hypersensitivity reactions to food proteins, normal bacterial flora and other environmental macromolecules. The interaction between epithelial cells and microflora is fundamental to establish gut mucosal barrier and GALT development. The normal colonization of intestine by commensal bacteria is thus crucial for a correct development of mucosal immune system. Probiotic bacteria are normal inhabitants of microflora and may confer health benefits to the host. The modification of the intestinal microflora towards a healthier probiotics enriched microflora may generate beneficial mucosal immunomodulatory effects and may represent a new strategy to cure intestinal and allergic diseases. The health benefits may be specific for different probiotic strains. Ongoing research is providing new insights into the probiotic beneficial effects and related mechanisms. This review represents an update of immunomodulatory activity of different probiotics and of the more accredited mechanisms underlying such activities. Presented at the Second Probiotic Conference, Košice, 15–19 September 2004, Slovakia.     

后生元缓解胃肠道疾病的研究进展及其潜在机制

胃肠道是全身代谢最活跃的器官之一，也是人体内最大的细菌库。人体胃肠道中含有丰富的微生物群，其与宿主健康存在着错综复杂的关系。肠道菌群处于一种动态平衡的状态，当这种平衡被打破时会引起便秘、腹泻、肠易激综合征、炎症性肠病和结直肠癌等胃肠道疾病的发生。近年来，关于后生元的研究越来越多，其对肠道屏障的保护作用与益生菌类似甚至效果更佳。本文重点介绍了当前后生元在动物实验和临床中改善胃肠道疾病的相关研究，探讨了后生元在胃肠道中的作用及其在增强上皮屏障、调节免疫系统、肠道菌群和神经系统4个方面的潜在作用机制。     

Exosome‐mediated effects and applications in inflammatory bowel disease

Gut mucosal barriers, including chemical and physical barriers, spatially separate the gut microbiota from the host immune system to prevent unwanted immune responses that could lead to intestinal inflammation. In inflammatory bowel disease (IBD), there is mucosal barrier dysfunction coupled with immune dysregulation and dysbiosis. The discovery of exosomes as regulators of vital functions in both physiological and pathological processes has generated much research interest. Interestingly, exosomes not only serve as natural nanocarriers for the delivery of functional RNAs, proteins, and synthetic drugs or molecules, but also show potential for clinical applications in tissue repair and regeneration as well as disease diagnosis and prognosis. Biological or chemical modification of exosomes can broaden, change and enhance their therapeutic capability. We review the modulatory effects of exosomal proteins, RNAs and lipids on IBD components such as immune cells, the gut microbiota and the intestinal mucosal barrier. Mechanisms involved in regulating these factors towards attenuating IBD have been explored in several studies employing exosomes derived from different sources. We discuss the potential utility of exosomes as diagnostic markers and drug delivery systems, as well as the application of modified exosomes in IBD.     

Immunology and probiotic impact of the newborn and young children intestinal microflora

Human body has developed a holistic defence system, which mission is either to recognize and destroy the aggressive invaders or to evolve mechanisms permitting to minimize or restore the consequences of harmful actions. The host immune system keeps the capital role to preserve the microbial intestinal balance via the barrier effect. Specifically, pathogenic invaders such as, bacteria, parasites, viruses and other xenobiotic invaders are rejected out of the body via barriers formed by the skin, mucosa and intestinal flora. In case physical barriers are breached, the immune system with its many components comes into action in order to fence infection. The intestine itself is considered as an “active organ” due to its abundant bacterial flora and to its large metabolic activity. The variation among different species or even among different strains within a species reflects the complexity of the genetic polymorphism which regulates the immune system functions. Additionally factors such as, gender, particular habits, smoking, alcohol consumption, diet, religion, age, gender, precedent infections and vaccinations must be involved. Hormonal profile and stress seems to be associated to the integrity microbiota and inducing immune system alterations. Which bacterial species are needed for inducing a proper barrier effect is not known, but it is generally accepted that this barrier function can be strongly supported by providing benefic alimentary supplements called functional foods. In this vein it is stressed the fact that early intestinal colonization with organisms such as Lactobacilli and Bifidobacteria and possibly subsequent protection from many different types of diseases. Moreover, this benefic microflora dominated but Bifidobacteria and Lactobacilli support the concept of their ability to modify the gut microbiota by reducing the risk of cancer following their capacity to decrease β-glucoronidase and carcinogen levels. Because of their beneficial roles in the human gastrointestinal tract, LAB are referred to as “probiotics”, and efforts are underway to employ them in modern nutrition habits with so-called functional foods. Members of Lactobacillus and Bifidobacterium genera are normal residents of the microbiota in the human gastrointestinal tract, in which they developed soon after birth. But, whether such probiotic strains derived from the human gut should be commercially employed in the so-called functional foods is a matter of debate between scientists and the industrial world. Within a few hours from birth the newborn develops its normal bacterial flora. Indeed human milk frequently contains low amounts of non-pathogenic bacteria like Streptococcus, Micrococcus, Lactobacillus, Staphylococcus, Corynebacterium and Bifidobacterium. In general, bacteria start to appear in feces within a few hours after birth. Colonization by Bifidobacterium occurs generally within 4 days of life. Claims have been made for positive effects of Bifidobacterium on infant growth and health. The effect of certain bacteria having a benefic action on the intestinal ecosystem is largely discussed during the last years by many authors. Bifidobacterium is reported to be a probiotic bacterium, exercising a beneficial effect on the intestinal flora. An antagonism has been reported between B. bifidum and C. perfringens in the intestine of newborns delivered by cesarian section. The aim of the probiotic approach is to repair the deficiencies in the gut flora and restore the protective effect. However, the possible ways in which the gut microbiota is being influenced by probiotics is yet unknown.     

益生菌与肠黏膜互作的分子机制研究进展

益生菌是一类定植于动物肠道,可辅助动物消化功能,维护肠道菌群平衡并可影响肠道免疫系统,有益于动物健康的重要调节性菌群。该类菌群与动物肠上皮细胞间互作的分子机制包括菌体表面分子如磷脂壁酸（phosphatidicacid,LTA）、表面层蛋白（Slayerprotein）等与宿主的粘附相关蛋白分子结合,通过占位效应抑制有害菌群在肠道内的定植;益生菌还可刺激肠道细胞分泌B防御素2、细菌素和有机酸等可抑制甚至杀灭有害菌群;在益生菌作用下,肠道上皮细胞可增强粘液糖蛋白、紧密连接蛋白occludin和ZO-1等分子的表达,加厚并加固肠道黏膜屏障;益生菌相关抗原可通过与抗原递呈细胞表面模式识别受体（TLRs等）分子结合,激活递呈细胞,启动各免疫细胞的交互作用,调节肠道免疫状态。     

Shuttling of information between the mucosal and luminal environment drives intestinal homeostasis

The gastrointestinal tract is a passageway for dietary nutrients, microorganisms and xenobiotics. The gut is home to diverse bacterial communities forming the microbiota. While bacteria and their metabolites maintain gut homeostasis, the host uses innate and adaptive immune mechanisms to cope with the microbiota and luminal environment. In recent years, multiple bi-directional instructive mechanisms between microbiota, luminal content and mucosal immune systems have been uncovered. Indeed, epithelial and immune cell-derived mucosal signals shape microbiota composition, while microbiota and their by-products shape the mucosal immune system. Genetic and environmental perturbations alter gut mucosal responses which impact on microbial ecology structures. On the other hand, changes in microbiota alter intestinal mucosal responses. In this review, we discuss how intestinal epithelial Paneth and goblet cells interact with the microbiota, how environmental and genetic disorders are sensed by endoplasmic reticulum stress and autophagy responses, how specific bacteria, bacterial- and diet-derived products determine the function and activation of the mucosal immune system. We will also discuss the critical role of HDAC activity as a regulator of immune and epithelial cell homeostatic responses.     

Microbiota-immune system interaction: an uneasy alliance

An estimated 100 trillion microbes colonize human beings, with the majority of organisms residing in the intestines. This microbiota impacts host nutrition, protection, and gut development. Alterations in microbiota composition are associated with susceptibility to various infectious and inflammatory gut diseases. The mucosal surface is not a static barrier that simply prevents microbial invasion but a critical interface for microbiota-immune system interactions. Recent work suggests that dynamic interactions between microbes and the host immune system at the mucosal surface inform immune responses both locally and systemically. This review focuses on intestinal microbiota-immune interactions leading to intestinal homeostasis, and show that these interactions at the GI mucosal surface are critical for driving both protective and pathological immune responses systemically.