肝硬化患者肠道菌群的研究

目的：研究肝硬化患者肠道苗群的变化 并分析血浆内毒素水平与肠道细菌的关系。方法：对37例肝硬化患者和18名健康者粪便中8种常见的厌氧菌及需氧菌进行定量研究，以偶氮基质显色法测外周血内毒素。结果：①肝硬化患者双歧杆菌、类杆菌、真杆菌的量明显低于正常组，而大肠杆菌，产气荚膜梭菌的量高于正常组（P<0．05)；②肝硬化患者肠菌失调程度与肝功能Child-Pugh分级有关；③肝硬化患者血浆内毒素水平与大脑杆菌量存在相关性。结论：肝硬化患者存在肠道菌群失调，具有代表性的厌氧菌减少，需氧菌增多。革兰阴性需氧杆菌大量繁殖可能是引起肝硬化肠源性内毒素血症的一个重要因素。     

肝硬化患者肠道菌群的研究

目的:研究肝硬化患者肠道菌群的变化、并分析血内毒素水平与肠道细菌的关系。方法:对37例肝硬化患者和18例健康者粪便中8种常见的厌氧菌及需氧菌进行定量研究,以偶氮基质显色法测外周血内毒素。结果:(1)肝硬化患者双歧杆菌、拟杆菌、真杆菌量明显低于正常组,而大肠杆菌、产气荚膜梭菌量高于正常组(P<0.05);(2)肝硬化患者肠菌失调程度与肝功能Child-Pugh分级有关;(3)肝硬化患者血内毒素水平与大肠杆菌量存在相关性。结论:肝硬化患者存在肠道菌群失调,具有代表性的厌氧菌减少,需氧菌增多。需氧革兰阴性杆菌大量繁殖可能是引起肝硬化肠源性内毒素血症的一个重要因素。     

肝炎后肝硬化患者肠道菌群变化初步分析

为了研究肝炎后肝硬化与肠道菌群间的关系，对４６名肝炎后肝硬化患者和５２名健康对照者进行了对比研究。方法为取０．５克新鲜粪便，用稀释液按１０倍稀释法将粪便稀释至１０－８，然后用滴注法接种于选择性培养基。选择肠道菌群中具代表性的需氧菌和厌氧菌共１０种。结果示：（１）实验组的肠杆菌、葡萄球菌、酵母菌、拟杆菌和双歧杆菌量明显低于对照组（Ｐ＜０．０１）。（２）伴腹泻者真杆菌减少，梭菌增加（Ｐ＜０．０５）。结果表明，肝硬化患者均有不同程度的肠菌群失调，而失调的程度往往与肝功能损害程度有关。     

脾虚泄泻患者肠道微生态学的初步研究

对３０例脾虚泄泻病人及２２例正常成年人粪便中的１０种厌氧菌、需氧菌进行定量研究。结果显示，脾胃虚弱型病人中，双歧杆菌、拟杆菌、消化球菌等厌氧菌明显减少；脾虚肝部型病人中，则肠杆菌相对增多。脾虚泄泻患者双歧杆菌（Ｂ）/肠杆菌（Ｅ）比值低于正常人。揭示厌氧菌减少、Ｂ／Ｅ值改变是牌失健运患者肠道微生态学主要特征。     

脾虚泄泻患者肠道微生态学的初步研究

对３０例脾虚泄泻病人及２２例正常成年人粪便中的１０种厌氧菌、需氧菌进行定量研究。结果显示，脾胃虚弱型病人中，双歧杆菌、拟杆菌、消化球菌等厌氧菌明显减少；脾虚肝郁型病人中，则肠杆菌相对增多。脾虚泄泻患者双歧杆菌（Ｂ）／肠杆菌（Ｅ）比值低于正常人。揭示厌氧菌减少、Ｂ／Ｅ值改变是脾失健运患者肠道微生态学主要特征。     

老年结直肠癌患者的肠道菌群检测结果分析

目的探讨老年结直肠癌患者的肠道菌群变化。方法选取2008年1月至2011年6月老年结直肠癌患者粪便标本50例及正常对照标本50例,运用传统梯度稀释法进行平板培养及提取粪便DNA后应用SYBRGreen I实时荧光定量PCR反应测定3种需氧菌和4种厌氧菌的数量以进行菌群分析。结果患者组粪便中需氧菌与厌氧菌菌群数与正常对照组比较均有明显改变。需氧菌中患者组金黄色葡萄球菌明显增加（P〈0．05）。厌氧菌中患者组双歧杆菌和乳酸杆菌均有程度不同的减少（P〈0．05）,在70岁以上老年患者中减少更明显;拟杆菌明显增加（P〈0．01）,在70岁以上老年患者中减少更明显。肠杆菌、肠球菌、小梭菌数量无明显差别（P〉0．05）。平板培养法与定量PCR法结果一致,PCR法较平板培养法更敏感。结论老年结直肠癌患者存在肠道菌群紊乱．其粪便中双歧杆菌及乳酸杆菌数量较正常对照明显减少,金黄色葡萄球菌和拟杆菌数量明显增多,随年龄增加菌群紊乱程度更严重,提示老年结直肠癌的发生、发展与肠道菌群有一定关系,针对性的补充益生菌可能是缓解病情的有效方法。     

肝硬化时腹水感染引起的自发性腹膜炎

126例肝硬化患者因腹水细菌感染而致自发性腹膜炎。最常见的致病菌为大肠杆菌(46％),此外为肺炎链球菌(17％)、其他种类的链球菌(17％)、肺炎杆菌(8％)、厌氧或微量需氧菌(6％)。肝硬化患者由厌氧菌或微量需氧菌引起的自发性腹膜炎,其腹部表现与需氧菌所致的相似,常有反跳痛或肠鸣音减弱。由需氧菌引起的肝硬化自发性腹膜炎118例中,只有一种病菌者108例(92％),有多种病菌者仅10例(8％),而8例厌氧菌所致的自发性腹膜炎中,有4例(50％)为多种细菌感染。需氧菌性自发性腹膜炎同时发生菌血症者52例(44％),而8例厌氧或微量需氧菌性自发性腹膜炎中,仅1例并     

肝硬化患者血清IL-6水平与腹水发生、内毒素血症及肠道细菌的关系

明确肝硬化患者血清IL．6水平与腹水发生、内毒素血症及肠道中大肠杆菌量的关系,并探讨其可能机制。方法：37例无感染征象的肝硬化患者纳入研究,18例健康者作为对照。分别以ELISA法、鲎试验及细菌培养法检测患者及对照者血清IL．6水平、血浆内毒素浓度及肠道太肠杆菌量。结果：肝硬化患者血清IL-6水平、血浆内毒素水平显著高于健康者。肝硬化伴腹水患者血清IL．6水平、粪太肠杆菌量均显著高于无腹水者,并发现血清IL-6水平与太肠杆菌量阃存在显著相关性。结论：肝硬化伴腹水患者血清IL-6水平显著升高,肠道中革兰阴性大肠杆菌的过度生长以及由此引起的细菌移位可能是导致此细胞因子高反应的重要因素,提示肝硬化患者血清IL-6水平可作为一个细菌移位的指标。     

嗜酸乳杆菌对肝硬化患者血氨和血浆内毒素水平的影响

目的：观察嗜酸乳杆菌制剂乐托尔胶囊对肝硬化患者肠道症状、血氨及血浆内毒素水平的影响。方法：Child-Pugh B级肝硬化患者24例，口服乐托尔胶囊（每次2粒，每日2次）3周，观察治疗前后相关临床症状、肝功能、血氨、血浆内毒素和细胞因子白细胞介素（IL）－1、IL－6水平的变化，并与双歧三联活菌胶囊培菲康治疗组（21例）和对照组（12例）进行比较。结果：乐托尔治疗组的腹泻、腹胀缓解病例数显著高于对照组（P＜0.01)，血氨、血浆内毒素显著降低的病例数亦明显高于对照组（P＜0.05)，肝功能、凝血酶原时间、IL－1、IL－6水平改善的病例数在两组间无明显差异。乐托尔治疗组和培菲康治疗组的各项症状和指标改善情况均无显著差异。结论：乐托尔胶囊可显著改善肝硬化患者的肠道症状，并能降低其血氨和血浆内毒素水平。     

消化道肿瘤患者肠道菌群的变化

目的探究消化道肿瘤患者肠道菌群的变化。方法选取消化道肿瘤患者的粪便标本,运用传统梯度稀释法进行细菌培养计数。结果消化道肿瘤患者与正常组相比,需氧菌中的肠球菌、大肠杆菌计数明显增多(P<0.05),葡萄球菌显著增加(P<0.01)。厌氧菌中的双歧杆菌、乳酸杆菌计数显著性减少(P<0.05),拟杆菌显著增加(P<0.01)。结论消化道肿瘤患者出现明显肠道菌群失调。     

肠黏膜通透性改变对肝硬化自发性细菌性腹膜炎的影响

目的探讨肠黏膜通透性改变对肝硬化自发性细菌性腹膜炎（SBP）的影响。方法 采用高压液相色谱-示差法，检测45例住院肝硬化腹水患者（34例白发性腹膜炎和11例肝硬化无菌性腹水）治疗前后口服糖分子探针乳果糖、甘露醇后尿液排泄率比值（LAC／MAN）情况，评估病人肠黏膜通透性水平；采用鲎试剂三肽显色基质偶氮法检测病人治疗前后血浆内毒素（LPS）水平，另11例健康志愿者作为对照组结果治疗前肝硬化SBP尿LAC／MAN、血浆内毒素水平均显著高于无菌性腹水（SA）组和健康对照组（P均〈0．001）Pearson相关性分析：肝硬化腹水患者尿LAC／MAN改变与血浆LPS水平呈正相关（r=0．187，P〈0．001）治疗1周后肝硬化SBP患者尿LAC／MAN及血浆LPS水平平行下降。结论肝硬化SBP患者存在肠黏膜通透性异常，且肠黏膜通透性改变与内毒素血症有关．     

肝硬化患者腹水中细菌DNA与相关因素的关系

目的 探讨肝硬化患者腹水中细菌DNA与血浆内毒素、肠通透性、肠道菌群等因素的关系. 方法 选取失代偿期肝硬化伴腹水患者55例,于入院当日或次日抽取腹水行腹水中细菌DNA的提取及PCR扩增,同时行腹水常规、需氧菌及厌氧菌培养检查,于入院次日测定血浆内毒素、肠通透性并进行肠道菌群分析,同时测定血常规、肝肾功能、凝血功能等生物化学指标.30例健康成年人作为正常对照,行除腹水之外的上述检查. 结果 55例肝硬化患者腹水细菌培养均为阴性,其中19例(34.55%)患者腹水中检测到细菌DNA.与细菌DNA阴性组比较,细菌DNA阳性组患者的凝血酶原活动度明显降低(t=-3.184,P=0.002),而肝功能Child-Pugh评分(t=3.224,P=0.002)和腹水白细胞计数(t'=4.088,P=0.001)明显升高.与正常对照组比较,肝硬化患者血浆内毒素水平(t=13.705,P=0.000)、尿中乳果糖/甘露醇(L/M,t'=28.568,P=0.000)和肠道肠杆菌数量(t=2.912,P=0.005)明显升高,而肠道双歧杆菌数量明显减少(t=-3.669,P=0.000).与腹水中细菌DNA相关的指标为肠道肠杆菌数量(P=0.007)和凝血酶原活动度(P=0.011).结论 肝硬化患者发生腹水细菌移位的关键因素是肠腔细菌过度生长,并与肝病的严重程度相关.     

肝硬化患者的内毒素和脂多糖结合蛋白水平及其与预后的关系

背景脂多糖结合蛋白(LBP)是介导脂多糖(LPS)活化单核/巨噬细胞的关键因子。尽管内毒素在慢性肝病和肝硬化中具有重要作用,但其结合蛋白在肝硬化中的意义尚不清楚。目的了解肝硬化患者的内毒素和LBP水平,并探讨其与预后的关系。方法分别以基质显色法鲎试验和酶联免疫吸附测定(ELISA)检测肝硬化患者的血浆内毒素和LBP水平;伴腹水患者同时测定腹水内毒素和LBP水平,并进行2个月的短期随访,记录存活情况。结果肝硬化患者的血浆内毒素和LBP水平均显著高于健康对照者(P<0.05),其中伴腹水患者的血浆内毒素水平显著高于无腹水患者(P<0.05)。Child鄄PughC级肝硬化伴腹水患者的腹水内毒素水平显著高于B级患者(P<0.05),而B级患者的血浆LBP水平显著高于C级患者(P<0.05)。短期随访显示肝硬化伴腹水死亡患者的腹水内毒素水平显著高于存活者(P<0.05)。结论肝硬化患者的血浆内毒素和LBP水平均升高,LBP水平升高可能是对肝硬化肠源性内毒素血症的一种持续的慢性炎症应答。腹水内毒素水平可以作为肝硬化伴腹水患者短期生存的一个预测指标。     

Intestinal bacterial overgrowth and bacterial translocation in cirrhotic rats with ascites

Background/Aims: Translocation of indigenous bacterial from the gut lumen of cirrhotic animals to mesenteric lymph nodes appears to be an important step in the pathogenesis of spontaneous bacterial peritonitis. However, the sequence of events leading to translocation remains unclear. One of the most predictable risk factors for translocation is overgrowth of gut bacterial flora. The present study was designed to compare the intestinal aerobic bacterial flora of cecal stools at the time of sacrifice between cirrhotic and normal rats and to evaluate the role of intestinal aerobic bacterial overgrowth in bacterial translocation in cirrhotic rats.Methods: Thirty-five male Sprague-Dawley rats with carbon tetrachloride-induced cirrhosis and ascites and 10 normal rats were included in this study. Cirrhotic rats were sacrificed when ill and samples of ascitic fluid, mesenteric lymph nodes and cecal stool were taken for detecting quantitatively aerobic bacteria.Results: Total intestinal aerobic bacterial count in cecal stool at the time of sacrifice was significantly increased in cirrhotic rats with bacterial translocation with or without spontaneous bacterial peritonitis compared to cirrhotic rats without bacterial translocation (p<0.001 and p<0.001, respectively) and to normal rats (p<0.001 and p<0.001, respectively). Of the 42 species of bacteria translocating to the mesenteric lymph nodes, 41 (97.6%) were found in supranormal numbers in the stool at the time of sacrifice.Conclusions: Carbon tetrachloride-induced cirrhotic rats with bacterial translocation have increased total intestinal aerobic bacteria count, and intestinal bacterial overgrowth appears to play an important role in bacterial translocation in this experimental model of cirrhosis in rats.     

小肠细菌过度生长相关性轻微肝性脑病患者的血浆内毒素水平

目的观察肝硬化患者小肠细菌过度生长相关性轻微肝性脑病患者的内毒素水平,探讨内毒素与轻微肝性脑病的关系。方法对90例肝硬化患者及20例健康志愿者进行内毒素水平、葡萄糖氢呼气试验（GHBT）、数字连接试验（NCT—A和NCT—BC）和数字符号试验（DST）检测,观察小肠细菌过度乍长相关性轻微肝性脑病患者的内毒素水平变化。结果肝硬化组小肠细菌过度生长（36．7％,33／90）明显高于健康对照组（5％,1／20）。20名健康志愿者未检出轻微肝性脑病（MHE）;90例肝硬化患者轻微肝性脑病37例（41．1％）,其中伴小肠细菌过度生长肝硬化患者轻微肝性脑病发生率高于不伴小肠细菌过度生长患者。肝硬化组内毒素水平（69．6±21．3）pg／mL高于健康对照组（18．7±8．6）pg／mL;肝硬化小肠细菌过度生长组内毒素水平（89．5±17．6）pg／mL高于无小肠细菌过度生长组（57．3±15．8）pg／mL（P〈0．05）。应用抗生素抑制小肠细菌过度生长及乳果糖治疗1周后GHBT、内毒素水平、NCT—A、NCT-BC及DST检查结果改善。结论内毒素与伴小肠细菌过度生长的轻微肝性脑病的发生及进展可能有一定的关系。     

肝硬化患者肠道菌群的初步分析及肠型分析

目的初步对肝硬化与肠道菌群的关系进行探讨并对肝硬化患者肠道菌群进行简单的肠型分析。方法纳入符合诊断标准的肝硬化患者80例,并选取同期健康志愿者40名。采用粪便细菌基因组DNA提取试剂盒采集肝硬化患者及健康志愿者的粪便,应用16s rDNA测序技术检测肠道菌群,并应用Qiime流程以及R软件等对测序结果进行分析。结果随着肝硬化的发生及严重程度的增加,致病菌如Escherichia/Shigella(埃希氏菌属/志贺氏菌属)、Streptococcus(链球菌属)、Veillonela(韦荣菌属)明显增加,而有益菌Prevoseburia(罗斯拜瑞氏菌属)、f_;achnospiraceae(毛螺旋菌科下的未知属)明显减少。其中,Escherichia/Shigella(埃希氏菌属/志贺氏菌属)的平均相对丰度百分比与Child-Pugh评分呈显著正相关。肠道菌群结构以Escherichia(埃希氏菌属)为主的人群罹患肝硬化且发展为重度肝硬化的风险更高。结论肝硬化的发生发展与肠道菌群密切相关且以Escherichia为主的肠道菌群结构为肝硬化的危险肠型。     

Role of intestinal bacterial overgrowth and intestinal motility in bacterial translocation in experimental cirrhosis.

BACKGROUND: Intestinal bacterial overgrowth (IBO) is related to small bowel motility and has been involved in the pathogenesis of bacterial translocation (BT) in experimental models, and both overgrowing gut flora and translocating bacteria to mesenteric lymph nodes are common features in cirrhosis. OBJECTIVES: The aims of this study were to analyze cecal aerobic bacteria and intestinal transit in cirrhotic rats, and their relationship with BT, evaluating the role of intestinal bacterial overgrowth and small bowel dismotility in the development of BT in experimental cirrhosis. MATERIAL AND METHODS: We included twenty-seven male Sprague-Dawley rats with carbon tetrachloride-induced cirrhosis without ascites and ten controls. Cultures of mesenteric lymph nodes (MLN), peripheral and portal blood, liver, spleen and cecal samples were carried out. Small intestinal transit was determined in ten cirrhotic rats and in ten control rats. RESULTS: The prevalence of bacterial translocation was 56%. Total cecal aerobic bacteria count was significantly higher in cirrhotic rats than in control rats (p < 0.001). Cirrhotic rats with translocated bacteria had higher total aerobic intestinal counts than culture-negative MLN bacteria (p < 0.05). The prevalence of total intestinal bacterial overgrowth in cirrhotic animals was 67%, and 0% in control animals (p < 0.001). According to BT, total IBO was more frequent in cirrhotic rats with BT versus those without BT (93 vs. 33%) (p < 0.001). Of the translocating bacteria, 95.6% were found to be overgrown in the cecum. The small-intestinal transit was slower in cirrhotic rats (60.5 +/- 12.7 cm vs. 81.2 +/- 5.7 cm) than in control animals (p < 0.001). CONCLUSIONS: These results suggest that the increase of intestinal aerobic bacteria in experimental cirrhosis is associated with translocation. In addition, IBO is frequent in cirrhotic rats, and is supposed to play an important role in the development of BT. Impaired motility of the small intestine is a common feature in cirrhosis and may be implicated in the pathogenesis of IBO.     

Gut flora and bacterial translocation in chronic liver disease

Increasing evidence suggests that derangement of gut flora is of substantial clinical relevance to patients with cirrhosis. Intestinal bacterial overgrowth and increased bacterial translocation of gut flora from the intestinal lumen, in particular, predispose to an increased potential for bacterial infection in this group. Recent studies suggest that, in addition to their role in the pathogenesis of overt infective episodes and the clinical consequences of sepsis, gut flora contributes to the pro-inflammatory state of cirrhosis even in the absence of overt infection. Furthermore, manipulation of gut flora to augment the intestinal content of lactic acid-type bacteria at the expense of other gut flora species with more pathogenic potential may favourably influence liver function in cirrhotic patients. Here we review current concepts of the various inter-relationships between gut flora, bacterial translocation, bacterial infection, pro-inflammatory cytokine production and liver function in this group.