腹部手术与肠道细菌移位和内源性感染

目的 人体肠道定植着大量的细菌,正常情况下肠道菌群与机体处于动态平衡,腹部外科手术的刺激和创伤可以破坏肠道正常的菌群结构和屏障功能,使细菌的数量、比例发生改变或空间上发生移位,引发内源性感染,最终导致机体各种功能障碍.研究分析腹部外科手术对肠道细菌及屏障功能的影响,为今后预防和治疗提供理论依据.     

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。     

肝硬化患者肠道菌群失衡的研究现状

肝硬化是我国的一种常见病,近年来越来越多的研究表明肝硬化及其并发症(如门静脉高压、自发性腹膜炎、肝性脑病及肝癌等)都与肠道菌群失衡有着密切的联系。肝脏和肠道通过"肠-肝轴"紧密联系在一起,肝硬化时因小肠细菌过度生长、肠黏膜屏障功能受损、机体免疫功能下降等因素,导致细菌移位、肠道微生态失衡。而肠道微生态失衡又会使肝功能障碍进一步发展,引起肝性脑病等并发症。本文就目前国内外对肝硬化及其并发症与肠道细菌及真菌菌群失衡的研究进行综述。     

应激状态下机体与肠道菌群的相互作用及天然多酚干预作用研究

机体长期处于应激状态下,导致焦虑和抑郁等精神疾病的发病率不断上升,严重威胁着人类健康和社会发展。许多研究表明应激会导致肠道菌群的紊乱,影响神经通路发生精神性疾病、使细菌移位产生免疫炎症。天然多酚类化合物具有多种生物活性,但绝大部分难以直接进入体内,而是在肠道中被肠道菌群降解。多酚可以调整机体应激反应状态下被扰乱的肠道菌群的组成和结构,使之恢复动态平衡,进而改善机体各种应激因素所致的焦虑和抑郁等症状。     

小鼠的免疫缺陷在其烫伤后引起肠道细菌易位的实验分析

近年来,创伤后肠道细菌易位引起的内源性感染日益受到重视。为了探讨细菌易位时免疫功能的作用,本文采用20%Ⅲ°烫伤的 T 细胞、NK 细胞,B 细胞免疫功能缺陷的与免疫功能正常的杂合子 SpF 小鼠进行实验,观察免疫功能缺陷时,伤后3个时相点中肠道细菌易位发生率,肠道微生态,回肠 MDA 和病理形态改变。获得;在肠道微生态未有改变,肠粘膜发生损伤的情况下,T 细胞和 NK 细咆免疫功能缺陷时,烫伤能促进肠道细菌易位,B 细胞免疫缺陷和免疫功能正常小鼠烫伤未发生肠道细菌易位。从机体的特异性和非特异性免疫的角度,对肠道正常菌丛易位引起的内源性感染进行了讨论。     

肠-肝轴与非酒精性脂肪性肝病

肠道菌群组成和数量的改变影响宿主的能量代谢、免疫应答和炎症反应状态。非酒精性脂肪性肝病患者常伴有小肠细菌过度生长或某些菌群种类和数量的改变,以及肠道黏膜通透性增加。肠道细菌通过增强肝脏脂肪合成、诱导机体胰岛素抵抗、激活天然免疫系统相关分子模式等机制,诱发肝脏炎症反应,启动纤维化进程,促进单纯性脂肪变向脂肪性肝炎发展。鉴定影响机体能量代谢和炎症反应的肠道菌群及其产物将为阐明肠-肝轴对肝脏炎症发生、发展所起的作用奠定基础,为揭示非酒精性脂肪性肝病发生、发展的机制开辟新思路,为该病的防治探索新策略。     

肠道细菌易位

人体肠道中有数百个种群、约 10 1 2 ～ 10 1 3 个细菌 ,重量可达 1公斤左右 ,这些细菌存在于特定的空间及时间 ,在数量上维持一定的比例 ,与人体相互依存 ,构成了人体肠道微生态系统。正常情况下 ,肠道细菌与机体处于动态平衡状态 ,一旦这一状态遭到破坏 ,就造成微生态失衡 ,表现为细菌种群数量及比例上的改变 (菌群失调 )或 /和细菌空间上的转移(移位或易位 ) ,导致各种疾病的发生及发展。肠道菌群失调在临床上较为常见 ,已广泛被人们认识 ,采用益生菌制剂防治也取得了显著的效果。而对肠道细菌易位的认识相对缓慢 ,可喜的是近十余年来 ,…     

综合养殖池塘中三角帆蚌和鱼类肠道细菌的组成

采用 PCR-DGGE (PCR-denaturing gradient gel electrophoresis)方法研究了综合养殖池塘中三角帆蚌(Hyriopsis cumingii)、草鱼(Ctenopharyngodon idella)、鳊(Parabramis pekinensis)、银鲫(Carassius auratus gibelio)、青鱼(Mylopharyngodon piceus)和鳙(Aristichthys nobilis)的肠道细菌组成,并分析了水体中的浮游细菌对鱼、蚌肠道细菌的影响。研究结果表明,三角帆蚌和混养鱼类肠道细菌属于厚壁菌门(Firmicutes)、变形菌门(Proteobacteria)、放线菌门(Actinobacteria)、疣微菌门(Verrucomicrobia)、蓝细菌(Cyanobacteria)、梭杆菌门(Fusobacteria)。其中,三角帆蚌肠道优势菌群为不动杆菌属(Acinetobacter)、志贺氏菌属(Shigella)和分枝杆菌属(Mycobacterium),草鱼肠道优势菌群为梭菌属(Clostridium),鳊肠道优势菌群为梭菌属和假单胞菌属(Pseudomonas),银鲫肠道优势菌群为不动杆菌属和志贺氏菌属,青鱼肠道优势菌群为梭菌属和不动杆菌属,鳙肠道优势菌群为不动杆菌属和弧菌属(Vibrio)。三角帆蚌与银鲫肠道细菌谱带相似性较高,草鱼与鳊肠道细菌谱带相似性较高,表明鱼类肠道细菌组成特点与食性存在一定的关系。水体浮游细菌优势菌群为类芽孢杆菌属(Paenibacillus)。三角帆蚌及鱼类肠道细菌群落与水体浮游细菌群落组成相似性较低,表明水体浮游细菌对三角帆蚌和鱼类肠道细菌优势菌群的影响有限。     

SD大鼠断奶后肠道菌群及肠道形态的变化

目的通过对断奶日龄不同的SD大鼠肠道菌群和肠道形态学指标变化的观察研究,为临床上研究肠道相关性疾病提供参考数据。方法选取断奶日龄为21 d的SD大鼠60只,雌雄各半,分别在断奶后第0、7、14、21、28天测定4种肠道正常菌群及肠道黏膜形态变化。结果SD大鼠断奶后不同时间点,不同肠段内大肠杆菌、双歧杆菌、乳酸杆菌和葡萄球菌呈现不同的变化规律,且断奶后第7天肠道细菌移位率明显提高,同时断奶后不同时间点,大鼠不同肠段黏膜厚度、肌层厚度、绒毛长度和宽度都呈现上升趋势。结论断奶后第7天和14天,SD大鼠肠道菌群和肠道形态学变化明显,且易发生肠道细菌移位。     

导读与评议(2017年第5期)

正正常人肠道内寄居着种类繁多的微生物,称为正常菌群。正常菌群间互相制约或依存,形成种类和数量相对平衡的状态。然而,在一定条件下如机体抵抗力下降或长期应用广谱抗生素,可因某些细菌大量繁殖,导致肠道菌群失调。测序、蛋白质组和转录组分析等组学研究技术的发展,进一步推动了肠道菌群的研究,人们开始关注和重视肠道菌群对宿主健康及疾病的影响。近年来还发现,肠道细菌可参与塑造大脑结构,影响人们的情绪、行为、感知,为揭示大脑功能与疾病的关系开辟了新思路,但也     

大鼠失血性休克后肠道微生态的改变

本研究对无特殊致病菌大鼠失血性休克后肠道微生态的改变及肠道细菌易位进行了动态观察。结果表明,失血性休克复苏后5小时,肠道微生态即发生改变,表现为回肠内肠杆菌菌量增多,肠道内类杆菌与肠杆菌菌量比值下降,而后这一改变随时间推移逐渐恢复;肠道细菌易位率也有类似变化,易位细菌以肠杆菌为主。结果提示,大鼠失血性休克后肠道细菌易位与肠道微生态的改变有密切关系。     

Bacteriophage translocation

The occurrence of phages in the human body, especially in the gastrointestinal tract, raises the question of their potential role in the physiology and pathology of this system. Especially important is the issue of whether phages can pass the intestinal wall and migrate to lymph, peripheral blood, and internal organs and, if so, the effects such a phenomenon could have (such passage by bacteria, known as bacterial translocation, has been shown to cause various disturbances in humans, from immune defects to sepsis). Available data from the literature support the assumption that phage translocation can take place and may have some immunomodulatory effects. In addition, phages of the gut may play a protective role by inhibiting local immune reactions to antigens derived from gut flora.     

乳酸杆菌制剂对应用抗生素大鼠体内TLR2 mRNA转录水平及相关因素影响的研究

目的动态观察乳酸杆菌制剂对应用抗生素大鼠肠道菌群结构和TLR2 mRNA转录水平的影响。方法采用细菌培养法定量检测肠道双歧杆菌、乳酸杆菌、肠杆菌和肠球菌;利用反转录聚合酶链反应技术测定大鼠肠黏膜组织、肠系膜淋巴结、肝脏和脾脏细胞TLR2 mRNA转录水平。结果应用抗生素可致肠道菌群失调和TLR2 mRNA转录水平的早期受抑制。乳酸杆菌制剂干预可迅速提高肠道乳酸杆菌数量,及早扶正肠道菌群结构,减轻由于应用抗生素引起的Toll样受体mRNA转录受抑程度。结论乳酸杆菌制剂早期干预可及早扶正肠道菌群结构,减轻TLR2 mRNA转录水平受抑制程度,为临床合理应用抗生素,早期益生菌干预提供理论依据。     

Bacterial translocation from the intestines

Bacterial translocation is defined as the passage of viable bacteria from the gastrointestinal (GI) tract through the mucosal epithelium to other sites, such as the mesenteric lymph nodes, spleen, liver and blood. This paper reviews results from animal models utilized to obtain information concerning the defense mechanisms operating in the healthy host to confine bacteria to the GI tract. Gnotobiotic and antibiotic-decontaminated mice colonized with particular bacteria demonstrated that the indigenous GI flora maintains an ecologic equilibrium to prevent intestinal bacterial overgrowth and translocation from the GI tract. Studies with athymic (nu/nu) mice, thymus-grafted (nu/nu) mice, neonatally thymectomized mice, and mice injected with immunosuppressive agents demonstrated that the host immune system is another defense mechanism inhibiting bacterial translocation from the GI tract. Ricinoleic acid given orally to mice disrupted the intestinal epithelial barrier allowing indigenous bacteria to translocate from the GI tract. Thus, bacterial translocation from the GI tract of healthy adult mice is inhibited by: (a) an intact intestinal epithelial barrier, (b) the host immune defense system, and (c) an indigenous GI flora maintaining ecological equilibrium to prevent bacterial overgrowth. Deficiencies in host defense mechanisms act synergistically to promote bacterial translocation from the GI tract as demonstrated by animal models with multiple alterations in host defenses. Bacterial translocation occurred to a greater degree in mice with streptozotocin-induced diabetes, mice receiving nonlethal thermal injury, and mice receiving the combination of an immunosuppressive agent plus an oral antibiotic than in mice with only a primary alteration in host defenses. The study of bacterial translocation in these complex models suggests that opportunistic infections from the GI tract occur in discrete stages. In the healthy adult animal, bacterial translocation from the GI tract either does not occur or occurs at a very low level and the host immune defenses eliminate the translocating bacteria. Bacterial translocation does take place if one of the host defense mechanisms is compromised, such as a deficiency in the immune response, bacterial overgrowth in the intestines, or an increase in the permeability of the intestinal barrier. In this first stage, the bacteria usually translocate in low numbers to the mesenteric lymph node, and sometimes spleen or liver, but do not multiply and spread systemically.(ABSTRACT TRUNCATED AT 400 WORDS)     

Gram-negative bacteria aggravate murine small intestinal Th1-type immunopathology following oral infection with Toxoplasma gondii

Oral infection of susceptible mice with Toxoplasma gondii results in Th1-type immunopathology in the ileum. We investigated gut flora changes during ileitis and determined contributions of gut bacteria to intestinal inflammation. Analysis of the intestinal microflora revealed that ileitis was accompanied by increasing bacterial load, decreasing species diversity, and bacterial translocation. Gram-negative bacteria identified as Escherichia coli and Bacteroides/Prevotella spp. accumulated in inflamed ileum at high concentrations. Prophylactic or therapeutic administration of ciprofloxacin and/or metronidazole ameliorated ileal immunopathology and reduced intestinal NO and IFN-gamma levels. Most strikingly, gnotobiotic mice in which cultivable gut bacteria were removed by quintuple antibiotic treatment did not develop ileitis after Toxoplasma gondii infection. A reduction in total numbers of lymphocytes was observed in the lamina propria of specific pathogen-free (SPF), but not gnotobiotic, mice upon development of ileitis. Relative numbers of CD4(+) T cells did not differ in naive vs infected gnotobiotic or SPF mice, but infected SPF mice showed a significant increase in the frequencies of activated CD4(+) T cells compared with gnotobiotic mice. Furthermore, recolonization with total gut flora, E. coli, or Bacteroides/Prevotella spp., but not Lactobacillus johnsonii, induced immunopathology in gnotobiotic mice. Animals recolonized with E. coli and/or total gut flora, but not L. johnsonii, showed elevated ileal NO and/or IFN-gamma levels. In conclusion, Gram-negative bacteria, i.e., E. coli, aggravate pathogen-induced intestinal Th1-type immunopathology. Thus, pathogen-induced acute ileitis may prove useful to study bacteria-host interactions in small intestinal inflammation and to test novel therapies based on modulation of gut flora.     

Effects of dietary antibiotics on intestinal microflora in broiler chickens

Changes were examined in the intestinal microflora in broiler chickens fed a diet containing antibiotics to obtain fundamental information on the mechanisms of beneficial effect of the antibiotics upon livestock production. Three antibiotics (colistin, bacitracin, and enramycin) were employed as feed additives. Experiments were conducted with broiler chickens in two ways. In one way dietary antibiotics were fed continually at levels approved for use as feed additives for a long term. In the other they were fed the same antibiotics for a short term. Significant changes in microflora were observed mainly in such bacterial groups as aerobic bacteria and Lactobacillus. In the long term administration, three possible modes of variance in the bacterial flora were postulated: Changes directly related to the antibacterial spectrum of antibiotics. Antagonistic changes related to an ecological balance in the bacterial flora. Changes in quantitative balance of bacteria constituting each bacterial group. The change in the intestinal microflora during administration of the antibiotic diet was expressed as a complex form of these transition modes. In the short term administration, it was demonstrated that the effect of the antibiotic diet lingered even 7 days after administration. This suggests that antibiotics used as feed additives may possibly affect the stability of the intestinal microflora.     

Green Fluorescent Protein Labeling Escherichia coli TG1 Confirms Intestinal Bacterial Translocation in a Rat Model of Chemotherapy

It has been reported that treatment with methotrexate (MTX) induces intestinal bacterial translocation; however, the definitive evidence of intestinal bacterial translocation induced by MTX has been lacking. The aim of this study was to confirm the intestinal bacterial translocation caused by MTX and to evaluate the preventive effect of granulocyte colony-stimulating factor (G-CSF) on intestinal bacterial translocation caused by MTX. Sprague-Dawley rats were treated with MTX (3.5 mg/kg) for 3 days to induce intestinal bacterial translocation; with gavaged Escherichia coli TG1 labeled with green fluorescent protein (GFP) for 2 days to track intestinal bacterial translocation; and with G-CSF (10 μg/kg) for 4 days to prevent intestinal bacterial translocation. Representative tissue specimens from the mesenteric lymph nodes, spleen, liver, and kidney were aseptically harvested for bacteria culture in ampicillin-supplemented medium. The bacteria labeled with GFP were detected in tissue specimens harvested from the rats treated with MTX but not detected in the rats that were not treated with MTX. G-CSF significantly ameliorated the situation of intestinal bacterial translocation.     

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。     

The intestinal flora: the scales without the sword

The intestine is colonised by a vast population of resident bacteria which have established mutualistic relationships with their host throughout evolution, progressing from commensalism to symbiotic interactions. Intestinal bacteria benefit from resources available in their host, but reciprocally provide advantages to their host, by supplying enzymatic activities not encoded in the host genome, by promoting maturation of the intestine and of the gut associated immune system as well as by modifying the host metabolism. The commensal bacteria, although deprived of pathogenic attributes, might however become a danger for the host in case of translocation, acquisition of pathogenic features or via the inappropriate activation of intestinal inflammation. Remarkably, the commensal flora promotes the onset of innate and adaptive immune defences which, in turn, allow to set up a subtle balance between the host and the flora that promotes the symbiosis.