肠道微生物-上皮细胞屏障互作的研究进展

肠道上皮细胞（intestinal epithelial cells,IECs）是动物机体抵御病原微生物的第一道防线,是黏膜机械屏障、免疫屏障和化学屏障的重要组成部分,具有吸收和屏障双层功能。肠道中微生物数量庞大、种类繁多,根据其与宿主的关系,主要分为共生菌、条件致病菌和病原菌3类,在肠道屏障的构建中发挥重要作用。IECs首先通过直接或间接方式对肠道微生物进行识别,区别自身与非自身,对自身物质（即共生菌）免疫耐受,对非自身物质（即病原菌）产生特异性免疫反应。IECs与肠道共生菌共同抵御肠道病原微生物,维持肠道健康,病原微生物侵入肠道,IECs主要通过胞外分泌物和细胞表面黏液层双重屏障发挥作用,其中胞外分泌物主要包括黏蛋白、抗菌分子和抗微生物免疫球蛋白。肠道共生菌可以通过竞争识别位点,分泌抗菌物质,增加黏液分泌,诱导IECs更新、增殖和修复等方式抵御病原微生物,维护正常的肠黏膜屏障功能。在IECs抵御肠道病原微生物入侵过程中,病原微生物通过自身运动、分泌毒素和酶等破坏肠上皮屏障,直接接触IECs,对其进行损伤。因此IECs和肠道菌群间相互作用,共同维持肠道内环境稳态。作者就IECs和肠道微生物结构、功能的适应性变化作一综述,以期阐述肠道微生物-上皮细胞屏障互作的机制。     

乳酸杆菌在调节肠道屏障功能中的作用

乳酸杆菌不仅是动物肠道内存在的正常微生物,也是益生菌的重要组成部分。肠道屏障主要是由肠道黏膜免疫系统组成的免疫屏障、肠黏液层和肠上皮细胞层组成的肠黏膜物理屏障及肠道微生物构成的生物屏障构成。作者综述了近年来国内外有关乳酸杆菌制剂对肠道屏障功能调控作用的研究进展。     

The effects of mycotoxins, fungal food contaminants, on the intestinal epithelial cell-derived innate immune response

Mycotoxins are structurally diverse fungal metabolites that can contaminate a variety of dietary components consumed by animals and humans. It is considered that 25% of the world crop production is contaminated by mycotoxins. The clinical toxicological syndromes caused by ingestion of moderate to high amounts of mycotoxins and their effect on the immune system have been well characterized. However, no particular attention has been focused on the effects of mycotoxins on the local intestinal immune response. Because of their location, intestinal epithelial cells (IECs) could be exposed to high doses of mycotoxins. As a component of the innate local immune response, intestinal epithelial cells have developed a variety of mechanisms which act to reduce the risk of infection by microorganisms or intoxication by toxic compounds. This review summarises the innate immune response developed by intestinal epithelial cells and reports the literature concerning the effects of mycotoxins on them. Particularly, the effects of mycotoxins on the maintenance of a physical barrier by epithelial cells will be discussed together with their effect on extrinsic protective components of the innate intestinal immunity: mucus secretion, antimicrobial peptide generation, IgA and pro-inflammatory cytokine release.     

益生菌对肠黏膜屏障的保护及作用机制研究进展

益生菌可以通过调节肠上皮细胞间紧密连接蛋白的表达,增加黏液分泌,抑制肠上皮细胞异常凋亡,激发肠黏膜免疫应答,从而保护肠黏膜屏障。对肠黏膜屏障的结构、病原菌对肠黏膜的损伤以及益生菌在受损肠黏膜保护及修复中的作用机制进行了综述,旨在阐明益生菌对维护机体健康的重要意义。     

分泌型IgA对肠道黏膜免疫的研究进展

分泌型IgA(secretory IgA,SIgA)作为一种包被于肠道黏膜的抗体,能保护肠道免受病原微生物和毒素的攻击而不引起炎症反应,对激活黏膜免疫和维持肠道内环境稳态起到重要作用。在动物肠腔中,SIgA能通过调节肠道上皮细胞受体的识别能力,阻断病原微生物侵入黏膜相关淋巴组织,随后在肠道蠕动和黏液绒毛的协助运动下,最终将病原微生物清除;且最近也有报道揭示SIgA在肠上皮胞吞转运作用下的新机制。因此,作者主要阐述SIgA在肠道黏膜免疫及其内环境方面发挥关键的生物学特征和功能,以及探讨胞吞转运机制下SIgA的潜在作用。     

丁酸介导下肠道菌群与宿主免疫互作机制的研究进展

肠道菌群或其代谢产物在动物机体生长发育与功能完善方面起重要作用,当宿主与肠道菌群间的动态平衡被打破,可诱发局部或全身性炎症反应。丁酸不仅作为能源物质为机体提供能量,还能调控宿主先天性免疫和适应性免疫状态,促进机体免疫应答;并影响宿主分泌抗菌肽（AMPs）等预防肠道病原菌易位,维持肠道菌群的稳态。本文将系统介绍丁酸介导下肠道菌群与宿主免疫系统间互作机制的研究进展,并阐明其在肠道健康稳态中的重要作用。     

丁酸钠对肉鸡肠道形态与消化吸收功能影响的研究进展

肠道是肉鸡重要的消化、内分泌及免疫器官，肠道健康主要依赖于营养物质、微生物菌群和肠道黏膜之间的动态平衡。肠道消化吸收功能与肠黏膜上皮细胞的生长及肠道形态结构的完整性直接相关。研究表明，丁酸钠作为能量来源，可刺激肉鸡肠道上皮细胞增殖并改善肠道黏膜形态，促进绒毛生长和肠道组织发育。丁酸钠通过肠道游离脂肪酸受体FFAR2和FFAR3介导肠道内分泌细胞分泌多种激素，促进胃肠黏膜的发育，刺激胃和胰腺分泌消化酶，促进养分消化吸收。丁酸钠是肠道稳态的重要调节因子，可刺激黏蛋白的产生，增加黏液层厚度，降低结肠上皮的通透性，维持肠道完整性和黏膜屏障功能。丁酸钠促进宿主防御肽（HPDs）的合成，抑制肠道内有害菌的增殖，降低内毒素对肠黏膜上皮细胞的损伤。丁酸钠通过抑制NF-κB激酶（IKK）下调促炎症途径，抑制NF-κB的活化，预防肠黏膜炎症发生，进而促进消化吸收和保护肠道健康。综上，丁酸钠具有肠道保护和抗菌作用，可增强肠道完整性，促进营养物质的消化吸收，提高免疫力和抗病力。在饲料工业禁抗的背景下，对抗生素替代品丁酸钠的研究和应用非常重要，作者就丁酸钠对肠道功能的作用机制进行重点阐述，以期为其在肉鸡饲料中替代抗生素提供科学依据。     

Probiotic alternatives to reduce gastrointestinal infections: the poultry experience

The intestinal mucosa represents the most active defense barrier against the continuous challenge of food antigens and pathogenic microorganisms present in the intestinal lumen. Protection against harmful agents is conferred by factors such as gastric acid, peristalsis, mucus, intestinal proteolysis, and the intestinal biota. The establishment of beneficial bacterial communities and metabolites from these complex ecosystems has varying consequences for host health. This hypothesis has led to the introduction of novel therapeutic interventions based on the consumption of beneficial bacterial cultures. Mechanisms by which probiotic bacteria affect the microecology of the gastrointestinal tract are not well understood, but at least three mechanisms of action have been proposed: production/presence of antibacterial substances (e.g., bacteriocins or colicins), modulation of immune responses and specific competition for adhesion receptors to intestinal epithelium. The rapid establishment of bacterial communities has been thought to be essential for the prevention of colonization by pathogenic bacteria. Some animal models suggest that the reduction in bacterial translocation in neonatal animals could be associated with an increase in intestinal bacterial communities and bacteriocin-like inhibitory substances produced by these species. This review emphasizes the role of the intestinal microbiota in the reduction of the gastrointestinal infections and draws heavily on studies in poultry.     

短链脂肪酸介导的宿主肠道免疫调控机制

肠道是营养素、微生物群和宿主进行免疫反应的共享场所。肠道稳态失衡、免疫功能失调、环境因素等都可能引发疾病,肠道微生物群是控制机体健康肠道内环境平衡的一个重要因素。短链脂肪酸(SCFAs)主要由细菌发酵产生,是肠道微生物群及宿主肠上皮细胞(IECs)的重要能量来源,能够维持肠道酸碱平衡,抑制有害病原菌生长,调节宿主肠道免疫,降低炎症反应。SCFAs不仅在共生细菌聚居的肠道内起局部作用,而且还影响肠道免疫细胞,调节免疫反应。本文主要概述了SCFAs通过G蛋白偶联受体(GPCRs)激活途径、组蛋白脱乙酰化酶(HDAC)抑制作用改变代谢状态,并将代谢途径与表观遗传修饰联系起来引起宿主免疫应答,降低肠道炎症反应并增强肠道屏障功能。     

Advances in Modulation of Intestinal Innate Defense Responses by Probiotic Bacteria

Probiotics are a kind of living microorganism which can be administered in feed and confer numerous health benefits to animals. Probiotics play a key role in maintaining the microbial balance of gastrointestinal, immunomodulation and pathogen defense, specific probiotics show certain degree of potential to reinforce the integrity of intestinal epithelium and regulate some immune components. The mechanism of probiotic action is an area of interest. Among all possible routes of modulation by probiotics of intestinal mediated defense responses, modulations of intestinal barrier function, innate and adaptive mucosal immune responses as well as signaling pathways are considered to play an important role in the intestinal defense responses against pathogenic bacteria. This review summarizes how probiotic bacteria interact with goblet cell-derived mucins, trefoil factors (TFFs),defensins, Toll-like receptors (TLRs), secretory immunoglobulin A (sIgA), heat shock proteins (HSPs) and P-glycoproteins (P-gp) in the gut to regulate the intestinal innate defense responses,which is regarded as the scientific basis for the future detailed study of benefits of probiotics towards the health of intestine and also dietary intervention against intestinal exposure to pathogens.     

益生菌对肠道先天防御反应调节作用的研究进展

益生菌是可添加在饲料中对动物健康产生很多益处的活微生物,其在维持胃肠道微生物平衡、免疫调节和病原体防御中起关键作用,某些特定的益生菌菌株对加强肠上皮的完整性和调节一些免疫组分也显示出一定程度的潜力。有关益生菌的作用机制是当前研究的热点,其中,在益生菌调节肠道介导的防御反应的所有可能途径中,肠屏障功能、先天和适应性黏膜免疫反应及信号传导途径被认为在针对病原菌的肠防御反应中起重要作用。作者主要针对益生菌如何与肠道内的杯状细胞黏蛋白、三叶因子（trefoil factors,tffs）、防御素、Toll样受体（Toll-like receptors,TLRs）、分泌型免疫球蛋白A（secretory immunoglobulin A,sIgA）、热休克蛋白（heat shock proteins,HSPs）和P-糖蛋白（P-glycoprotein,P-gp）相互作用而起到调节肠道先天防御反应的作用进行了概述,以期为今后研究益生菌对肠道健康及对感染病原体的肠道如何起到有益作用奠定基础。     

Enteric bacteria: Friend or foe?

The normal gastrointestinal tract contains an enormous number of aerobic and anaerobic bacteria which normally enjoy a symbiotic relationship with the host but can have adverse effects with local and systemic consequences. The small intestine constitutes a zone of transition between the sparsely populated stomach and the luxuriant bacterial flora of the colon. Regulation of the intestinal flora depends on complex interactions between many factors including secretion of gastric acid, intestinal motility, biliary and pancreatic secretions, local immunity, the surface glycocalyx and mucus layer, and diet. Microbial interactions are also important, and can involve alterations in redox potential, substrate depletion and production of substances such as bacteri-ocins that inhibit bacterial growth. The beneficial effect of the normal enteric flora include the competitive exclusion of potentially pathogenic organisms, and the production of nutrients such as short-chain fatty acids (which represent an important energy source for the colonic mucosa) and vitamins. Detrimental effects of the enteric flora include competition for calories and essential nutrients, particularly by bacteria located in the small intestine, and a capacity to damage the mucosa, in some circumstances causing or contributing to inflammatory bowel disease. These problems can be accentuated by interference with the physiological regulation of intraluminal bacteria allowing overgrowth by a normal resident, or colonisation by transient pathogens. The pathophysiological consequences may involve direct damage to the intestinal mucosa, and bacterial metabolism of intraluminal constituents, for example forming deconjugated bile acids and hydroxylated fatty acids which stimulate fluid secretion. Additional problems arise if there is interference with the mucosal barrier since this can result in increased passage of bacteria and bacterial products stimulating mucosal inflammation, while bacterial translocation can result in bacteraemia and septicaeniia. Problems associated with bacterial pathogens are illustrated by the properties of the spectrum of pathogenic Escherichia coli, some of which facilitate long-term colonisation by adherence to the surface or invasion of enterocytes.     

Health-beneficial effects of probiotics: Its mode of action

It is now widely recognized that probiotics have health-beneficial effects on humans and animals. Probiotics should survive in the intestinal tract to exert beneficial effects on the host's health. To keep a sufficient level of probiotic bacteria in the gastrointestinal tract, a shorter interval between doses may be required. Although adherence to the intestinal epithelial cell and mucus is not a universal property of probiotics, high ability to adhere to the intestinal surface might strongly interfere with infection of pathogenic bacteria and regulate the immune system. The administration of probiotic Lactobacillus stimulated indigenous Lactobacilli and the production of short-chain fatty acids. This alteration of the intestinal environment should contribute to maintain the host's health. The immunomodulatory effects of probiotics are related to important parts of their beneficial effects. Probiotics may modulate the intestinal immune response through the stimulation of certain cytokine and IgA secretion in intestinal mucosa. The health-beneficial effects, in particular the immunomodulation effect, of probiotics depend on the strain used. Differences in indigenous intestinal microflora significantly alter the magnitude of the effects of a probiotic. Specific probiotic strains suitable for each animal species and their life stage as well as each individual should be found.     

乳酸杆菌益生作用机制的研究进展

乳酸杆菌作为益生菌广泛用于人和动物。本文综述了乳酸杆菌改善宿主健康的机制。乳酸杆菌可通过产生抗菌物质如乳酸、过氧化氢、细菌素,或者通过竞争营养或肠道黏附位点来抑制致病菌;通过诱导黏附素的分泌或阻止细胞凋亡而增强肠道的屏障功能,从而保护肠道。文章重点讨论了乳酸杆菌表面成分（表面蛋白、脂磷壁酸和肽聚糖）与肠道受体（Ｃ型凝集素受体、Ｔｏｌｌ样受体和 Ｎｏｄ样受体）,阐述了他们结合后启动免疫调节信号,调控肠道免疫功能以发挥改善健康作用的机制。     

Gene expression study of two widely used pig intestinal epithelial cell lines: IPEC-J2 and IPI-2I

The intestinal epithelial cells (IEC) play an important role in the immune system of swine, protecting against infectious and non-infectious environmental insults. The IEC participate in the innate immune response of the intestine through different mechanisms such as barrier function, mucus secretion, antibacterial peptide synthesis and participation in the cytokine/chemokine networks.Most of the current knowledge of intestinal cell functions has come from studies conducted on cell cultures generated from human cancers or from classical animal models. However, because the molecular and cellular elements of the immune system have been selected over evolutionary time in response to the species-specific environment, models of immune function based on mouse and human need to be applied cautiously in pig. Few models of swine small intestine epithelium exist and these are poorly characterised. In the present study we characterised the basal expression of epithelial and immune-related genes of two pig small intestine cell lines, IPEC-J2 and IPI-2I, under different culture conditions. These data represent essential background information for future studies on pig-intestinal pathogen interactions.     

Immunologic structures and functions of the gut

The intestine is richly populated with lymphoid tissue capable of initiating and effecting a wide variety of immunologic reactions. These reactions have consequences not only for the gut itself but for the body in general, and have established the importance of the gut as an immunologic organ. Among the outer and inner surfaces of our body, the 200 to 300 m2 of the gut contrast with the 2 m2 of the skin, and the 80 m2 of the lung. At the inner surface of the intestine, our organism contacts intimately bacteria, parasites, enzymes, toxins, a wide variety of dietary substances and their breakdown products. The essential barrier against the permanent antigenic burden is the mucosa. Its integrity depends on the continual replication, maturation, and metabolism of its constituents. Additional defense functions are exerted by the mucus, lysozyme, phagocytes, other cells, humoral factors and biological response modifiers involved in inflammatory and immune reactions. Some of these factors are being produced very close to the surface at which they act. The sum of the mechanical, humoral, cellular, immunologic and non-immunologic defense factors of the intestinal mucosa constitutes the mucosal block. However, the block is not complete. Rather, a continuous antigenic uptake through the epithelial layer takes place. The specialized structures of Peyer's patches, solitary lymph follicles, appendix vermiformis and their associated epithelium allow a controlled antigen uptake (sampling). Because of the heavy antigenic load, the intestine can be described as the most important immunologic contact organ of our body. The antigens may give rise to local and systemic immune reactions with antibody production, or the suppression of systemic immunologic responses to ingested antigens ("oral tolerance").     

动物肠上皮细胞体外模型用于中药作用机制研究进展

肠上皮细胞(IECs)体外模型广泛用于肠道致病菌菌株、药物、食品的细胞毒性评估和作用机理研究。通过测定相关指标的变化评价细胞毒性、细胞完整性及屏障功能,分析信号通路中特定蛋白水平探讨药物作用的信号通路及其作用机制,由于许多中药的作用机制至今尚不清晰,在治疗和预防相关疾病时尚未有明确的理论支持。论文通过对多酚类、多糖类、生物碱类、皂苷类及中药方剂在IECs中的作用机制的研究进行综述,以期为未来中药治疗和预防胃肠相关疾病的研究提供理论基础。     

Role of intestinal epithelial cells in the innate immune defence of the pig intestine

The intestinal epithelium serves as a dynamic barrier, which in the course of its normal function, maintains regulated uptake of nutrients and water while excluding potential pathogens. Over the past decade many studies have also revealed the immunological importance of intestinal epithelial cells (IEC). IEC have developed a variety of mechanisms to reduce the risk of infection by invasive pathogens or damage by toxic compounds. The effective maintenance of a physical barrier function is dependent on the establishment of well-organised intercellular junctions and a constant state of regeneration/renewal of the epithelium. IEC also participate in the innate immune responsiveness of the intestine by their ability to secrete mucus and antimicrobial peptides. IEC are also able to secrete cytokines and to respond to exogenous chemokines. This review summarises the current knowledge of the innate immune mechanisms developed by porcine IEC.     

A newly established bovine intestinal epithelial cell line is effective for in vitro screening of potential antiviral immunobiotic microorganisms for cattle

We evaluated whether a bovine intestinal epithelial (BIE) cell line could serve as a useful in vitro model system for studying antiviral immune responses in bovine intestinal epithelial cells (IECs) and for the primary screening of immunobiotic microorganisms with antiviral protective capabilities. Immunofluorescent analyses revealed that toll-like receptor 3 (TLR3) was expressed in BIE cells, and the results of real-time quantitative PCR showed that these cells respond to stimulation with poly(I:C) by up-regulating pro-inflammatory cytokines and type I interferons. In addition, we demonstrated that BIE cells are useful for the primary screening of immunobiotic lactic acid bacteria strains which are able to beneficially modulate antiviral immune responses triggered by TLR3 activation in bovine IECs. The characterization of BIE cells performed in the present study represents an important step towards the establishment of a valuable bovine in vitro system that could be used for the development of immunomodulatory feed for bovine hosts.     

丁酸钠对鱼类肠道消化吸收的影响研究进展

与畜禽等动物相比,鱼类消化系统不健全,消化酶活性低,而植物性原料中常含有抗营养因子和毒性成分等,易导致肠道损伤及肠炎等疾病。丁酸等短链脂肪酸可显著改善鱼类生长性能,增强鱼体健康及抗氧化和抗应激能力。因丁酸气味不佳,影响动物适口性,丁酸钠作为丁酸的替代物,呈固态且不易挥发,易于添加使用。丁酸钠可促进肠道上皮细胞发育,改善肠道形态结构,保持肠道黏膜屏障完整,对损伤的肠道黏膜加以修复,刺激上皮细胞内mRNA和蛋白质合成,加速肠上皮细胞增殖,增加绒毛高度,促进消化吸收。丁酸钠能破坏有害菌DNA结构,蛋白质不能合成,使有害菌不能进行正常分裂,抑制肠道有害菌的生长繁殖,促进有益菌群的增殖,维持肠道菌群平衡,菌群多样性显著提高。丁酸钠可通过刺激消化酶的分泌来改善鱼类消化,降低劣质蛋白原料对肠道损伤,抑制鱼肠道细胞凋亡,减少肠道炎症发生,显著改善鱼类肠道屏障的功能。丁酸钠还可用作生长促进剂及免疫刺激剂,在低鱼粉饲料中使用可降低饲料成本,促进鱼类生长发育。因此,丁酸钠是绿色安全可替代抗生素的添加剂,同时植物蛋白适当替代鱼粉可提高经济效益。作者就丁酸钠对肠道消化吸收功能的影响进行重点阐述,以期为鱼类等水产...