枯草杆菌肠球菌二联活菌胶囊对非酒精性脂肪性肝炎肠道菌群失调的干预作用

目的:探讨枯草杆菌肠球菌二联活菌胶囊对非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)患者肠道菌群失调的干预作用.方法:选择肠道菌群中具有代表性的细菌共8种(肠杆菌、肠球菌、葡萄球菌、双歧杆菌、乳杆菌、拟杆菌、梭菌、酵母样真菌)进行培养和计数,检测所有被研究者的血清内毒素、TNF-α、IL-6和ALT的浓度.选择健康正常成人30例作为正常对照组(A组),NASH共60例,随机分为常规治疗组(B组)和观察组(C组)各30例,B组采用常规保肝治疗,C组常规保肝治疗的同时联用枯草杆菌肠球菌二联活菌胶囊治疗,治疗4wk,比较各组治疗前后肠道细菌数量的变化和内毒素、TNF-α、IL-6、ALT的变化,并比较B组和C组治疗后临床症状的缓解情况.结果:与A组比较,治疗前NASH组肠杆菌显著增多(7.28±1.22 vs 6.54±1.08,t=4.83,P<0.01),而双歧杆菌、乳酸杆菌、拟杆菌显著减少(7.13±1.28 vs 8.83±1.24,t=-6.65,P<0.01;6.67±1.21 vs 7.31±1.12,t=-2.16,P<0.05;6.99±1.31 vs 7.82±1.15,t=-2.41,P<0.05);血清中内毒素、IL-6、TNF-的浓度显著增高(168.37EU/L±24.13EU/L vs 110.53EU/L±18.33EU/L,t=11.69,P<0.01;42.62ng/L±12.65ng/L vs 21.58ng/L±8.47ng/L,t=7.71,P<0.01;15.98ng/L±3.19ng/L vs 8.63ng/L±2.49ng/L,t=11.97,P<0.01);C组治疗后与治疗前比较双歧杆菌、乳杆菌、拟杆菌的数量显著增多(P<0.01),肠杆菌的数量显著减少(P<0.05),血清中内毒素、TNF-α、IL-6、ALT的浓度显著降低(P<0.01),C组治疗后临床症状较B组有显著改善.结论:NASH患者存在肠道菌群失调、革兰氏阴性杆菌过度生长,提示肠道微生态失衡可能参与了NASH的发生发展.枯草杆菌肠球菌二联活菌胶囊可明显改善NASH肠道菌群失调,降低血清中内毒素、TNF-α、IL-6、ALT的水平,改善临床症状.     

双歧三联活菌对大鼠非酒精性脂肪性肝炎作用的实验研究

目前,非酒精性脂肪性肝炎(non-alcohol steatohepatitis,NASH)的发病率逐年升高[1,2].其与肠道菌群失调、肠源性内毒素血症(intestinal endotoxemia,IETM)的关系也日益成为关注焦点.本研究旨在应用双歧三联活菌调整大鼠肠道菌群、恢复肠黏膜屏障,继而减轻IETM,进一步观察NASH模型大鼠肝脏病理学变化.     

乳果糖降低非酒精性脂肪性肝炎患者肠道通透性及血清内毒素水平

目的探讨乳果糖对非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)患者肠道通透性的干预作用。方法选择健康正常成人30例作为正常对照组(A组),非酒精性脂肪性肝炎共60例,随机分为NASH对照组(B组)和乳果糖干预组(C组)各30例,其中C组给予乳果糖(10 mL/d)进行干预。检测所有被研究者的血清内毒素、二胺氧化酶(diamine oxidase,DAO)、D-乳酸及ALT的浓度。干预4周后,再次检测B、C两组的血清内毒素、二胺氧化酶(DAO)、D-乳酸及ALT的浓度。结果与A组比较,治疗前B、C两组内毒素、DAO、D-乳酸水平显著增高(P<0.01),B组干预前后比较,内毒素、DAO、D-乳酸及ALT水平无显著改变(P>0.05),而C组干预前后比较,内毒素、DAO、D-乳酸及ALT水平显著降低(P<0.01)。结论 NASH患者血清内毒素水平及肠道通透性增高,乳果糖可降低NASH患者肠道的通透性及血浆内毒素水平。     

非酒精性脂肪性肝病患者肠道微生态差异性及其与糖脂代谢相关指标的关系

目的分析非酒精性脂肪性肝病(NAFLD)患者肠道微生态差异性及其与糖脂代谢相关指标的关系。方法选择2017年6月至2019年4月三二〇一医院收治的NAFLD患者121例为观察组,同期选择100例健康体检患者为对照组,将观察组患者根据临床分型分为单纯性脂肪肝组(n=50)、非酒精性脂肪性肝炎(NASH)组(n=40)和肝硬化组(n=31)。观察各组肠道微生物、糖脂代谢相关指标水平,并分析肠道微生物与糖脂代谢相关指标相关性。结果观察组肠杆菌、肠球菌、酵母样真菌数量高于对照组,且双歧杆菌、乳酸杆菌数量低于对照组(P<0.05);观察组FBG、FINS、TG、TC、LDL-C指标高于对照组,且HDL-C低于对照组(P<0.05);肝硬化组肠杆菌、肠球菌、酵母样真菌数量高于单纯性脂肪肝组、NASH组,且双歧杆菌、乳酸杆菌数量低于单纯性脂肪肝组、NASH组(P<0.05);NASH组肠杆菌、肠球菌、酵母样真菌数量高于单纯性脂肪肝组,且双歧杆菌、乳酸杆菌数量低于单纯性脂肪肝组(P<0.05);肝硬化组FBG、FINS、TG、LDL-C指标高于单纯性脂肪肝组、NASH组,且TC、HDL-C低于单纯性脂肪肝组、NASH组(P<0.05);NASH组FBG、FINS、TG、LDL-C指标高于单纯性脂肪肝组,且TC、HDL-C低于单纯性脂肪肝组(P<0.05);糖脂代谢指标与肠球菌、肠杆菌、酵母样真菌数量呈正相关,与乳酸杆菌、双岐杆菌数量呈负相关(P<0.05)。结论NAFLD患者较单纯性脂肪肝患者肠道微生态、糖脂代谢具有显著差异,且两者有一定相关性。     

枯草杆菌肠球菌二联活菌胶囊对非酒精性脂肪性肝炎患者血清内毒素水平的影响

目的探讨枯草杆菌肠球菌二联活菌胶囊对非酒精性脂肪性肝炎(NASH)患者肠道通透性及血清内毒素水平的影响。方法选择健康正常成人30例作为正常对照组和非酒精性脂肪性肝炎患者60例,给予后者枯草杆菌肠球菌二联活菌胶囊治疗4周。检测所有被研究者血清内毒素、二胺氧化酶(DAO)、D-乳酸及ALT水平。结果与对照组比较,治疗前患者内毒素、DAO、D-乳酸水平显著增高【分别为143.60±21.41EU/l对109.78±17.81EU/l(t=7.71,P<0.01);2.6±0.47U/ml对2.3±0.48U/ml(t=2.24,P<0.05);6.1±1.05mg/l对5.3±0.97mg/(l t=4.89,P<0.01)】;NASH患者治疗后与治疗前比较,内毒素、DAO、D-乳酸及ALT水平显著降低。结论非酒精性脂肪性肝炎患者肠道通透性及血清内毒素水平增高,微生态制剂枯草杆菌肠球菌二联活菌胶囊可降低肠道通透性、血清内毒素及ALT水平。     

靶向肠道菌群代谢产物防治非酒精性脂肪性肝病*

<正>非酒精性脂肪性肝病(NAFLD)是以肝脏脂质沉积为特点的慢性疾病,疾病谱包括单纯性脂肪肝、非酒精性脂肪性肝炎(NASH)及其相关肝硬化和肝细胞癌。NASH是NAFLD的严重类型,NASH相关的肝脏炎症很难自行缓解,目前尚缺乏有效的治疗手段~([1])。肠道菌群与宿主的代谢状况密切相关~([2]),肠道菌群紊乱在NAFLD的发生发展中起着重要作用~([3,4])。除了肠道菌群本身,基于肠道菌群分泌、修饰和降解的代     

慢性肝病患者在疾病恢复期肠道菌群状况的研究

目的 了解慢性肝病患者在疾病恢复期肠道菌群的变化.方法 选择肠道菌群中具有代表性的细菌共5种进行培养和计数.结果 处于疾病恢复期的入选病例中肠道菌群失调的发生率为82.72%.结论 慢性肝病患者在疾病恢复期存在肠道菌群失调.     

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。     

肠道菌群与非酒精性脂肪性肝炎发生发展的关系

目前非酒精性脂肪性肝炎(NASH)的发生机制仍不明确,经典的"二次打击"学说不能解释所有NASH的产生,对于肠道菌群改变与NASH发生、发展过程中的关系近些年越来越受重视。肠道菌群导致的能量代谢紊乱、脂多糖内毒素血症、内源性乙醇产生增加、胆汁酸代谢紊乱、胆碱代谢改变、免疫调控障碍等多个方面与NASH发生存在一定关系。综述了肠道菌群在NASH发生、发展过程中的作用。     

噻唑烷二酮类对NASH的作用——系统回顾和荟萃分析

非酒精性脂肪性肝病(NAFLD)被认为是代谢综合征在肝脏的一个表现,普遍认为和胰岛素抵抗(IR)有关,当存在二次(或多次)打击,包括氧化应激、内质网应激、游离脂肪酸的脂毒性、细胞因子和肠道菌群失调等,就会导致细胞脂肪变性、炎症坏死和疾病的进展(综合反应假说),即处于非酒精性脂肪性肝炎(NASH)状态.     

Leaky gut and the liver: a role for bacterial translocation in nonalcoholic steatohepatitis

Gut flora and bacterial translocation (BT) play important roles in the pathogenesis of chronic liver disease, including cirrhosis and its complications. Intestinal bacterial overgrowth and increased bacterial translocation of gut flora from the intestinal lumen predispose patients to bacterial infections, major complications and also play a role in the pathogenesis of chronic liver disorders. Levels of bacterial lipopolysaccharide, a component of gram-negative bacteria, are increased in the portal and/or systemic circulation in several types of chronic liver disease. Impaired gut epithelial integrity due to alterations in tight junction proteins may be the pathological mechanism underlying bacterial translocation. Preclinical and clinical studies over the last decade have suggested a role for BT in the pathogenesis of nonalcoholic steatohepatitis (NASH). Bacterial overgrowth, immune dysfunction, alteration of the luminal factors, and altered intestinal permeability are all involved in the pathogenesis of NASH and its complications. A better understanding of the cell-specific recognition and intracellular signaling events involved in sensing gut-derived microbes will help in the development of means to achieve an optimal balance in the gut-liver axis and ameliorate liver diseases. These may suggest new targets for potential therapeutic interventions for the treatment of NASH. Here, we review some of the mechanisms connecting BT and NASH and potential therapeutic developments.     

非酒精性脂肪性肝病对肠道菌群多样性影响的初步研究

目的通过高脂饮食建立非酒精性脂肪性肝病(NAFLD)大鼠模型,观察NAFLD对肠道菌群多样性及群落组成的影响。方法建立NAFLD大鼠模型,通过大鼠肝脏病理切片HE染色验证NAFLD模型的成立,利用16sRNA测序技术对粪便肠道微生物进行检测分析,探讨NAFLD对肠道菌群多样性及群落组成的影响。结果肝脏组织学检查显示NAFLD组大鼠肝脏脂肪变明显,提示NAFLD动物模型建立成功。对照组Shannon多样性指数显著高于NAFLD组(P0.05)。提示对照组的肠道微生物多样性显著丰富于NAFLD组。在门水平的变化情况提示,与对照组相比,NAFLD组中厚壁菌门和变形菌门的相对丰度较高(均P0.05),而拟杆菌门的相对丰度则较低(P0.05)。在科水平的变化情况提示,正常对照组以毛螺菌科、瘤胃球菌科、拟杆菌科_S24-7为优势菌科,而NAFLD组则以毛螺菌科、瘤胃球菌科为优势菌科。与对照组相比,NAFLD组中的毛螺菌科、拟杆菌科、脱硫弧菌科、氨基酸球菌科、Christensenellaceae菌科等相对含量较高(均P0.05),而拟杆菌科_S24-7、普雷沃氏菌科、乳杆菌科等相对含量较低(均P0.05)。结论 NAFLD可降低肠道菌群的多样性,并且显著改变肠道菌群的组成和含量。     

Innate Immune Reactivity of the Ileum–Liver Axis in Nonalcoholic Steatohepatitis

Background  

Over-proliferation and bacterial translocation of Gram-negative bacilli within the intestinal flora, and increased portal venous levels of endotoxins, are involved in nonalcoholic steatohepatitis (NASH).     

Obesity and female gender increase breath ethanol concentration: potential implications for the pathogenesis of nonalcoholic steatohepatitis

OBJECTIVES: Similarities between histological features of alcoholic hepatitis and obesity-related liver disease suggest a common pathogenic mechanism. Because intestinal bacteria can produce ethanol, it is conceivable that intestinally derived alcohol may contribute to fatty liver disease. An indirect way of measuring endogenous ethanol is to measure the breath ethanol concentration. In a previous study in ob/ob mice, breath ethanol decreased with a course of non-absorbable antibiotics, suggesting that the ethanol is derived from intestinal bacterial flora. The aims of this study were 1) to determine whether alcohol can be detected in the breath of human subjects, and 2) to assess whether there is any correlation between ethanol and obesity in patients with nonalcoholic steatohepatits (NASH) and control subjects without known liver disease. METHODS: Breath ethanol concentration was determined in 21 patients with biopsy-proven NASH and in 10 control subjects by gas chromatography. An abnormal breath ethanol level was defined as two standard deviations above the mean value of the breath ethanol of lean controls. RESULTS: Minute quantities of ethanol were detected in the breath of human subjects who had not consumed alcohol in the recent past. Patients who were obese were more likely to have higher breath ethanol concentrations. Women also had higher breath alcohol than men. However, there was no difference between patients with NASH and controls. Severity of liver disease, as evidenced by cirrhosis, did not influence the breath ethanol concentration. CONCLUSIONS: Higher breath ethanol concentrations are observed in obese subjects than in leaner ones. It is possible that intestinally derived ethanol may contribute to the pathogenesis of NASH.     

非酒精性脂肪性肝炎临床特征及其危险因素分析

目的探讨非酒精性脂肪性肝炎（NASH）的临床特征及其危险因素。方法选取NASH患者76例和健康人84例,分析临床症状、生化和影像学指标。结果在76例患者中,体检发现者43例（56.6%）,有症状者33例（43.4%）;NASH组BMI、DBP、FPG、2hPPG、TG、ALT、ALT/AST、CRP、PLT与对照组比较有显著性差异（P〈0.05）;与NASH关系最密切的指标是BMI（OR=8.45）,其次分别是TG、2hPPG、FPG、DBP、年龄、病程（OR分别为3.70,2.83,2.61,2.10,1.41、1.20）。结论 NASH患者起病隐匿,多无明显的消化道症状,肥胖、高脂血症、糖尿病和高血压是发生NASH的主要危险因素。     

乙型肝炎肝硬化患者肠道菌群变化研究*

目的 分析乙型肝炎肝硬化患者肠道菌群的分布情况及其临床意义。方法 2018年 7月～2019年4月我院收治的乙型肝炎肝硬化患者103例(代偿期肝硬化41例和失代偿期肝硬化62例)和同期健康人群20例,采集粪便,采用Illumina Miseq测序法分析肠道菌群结构差异和物种多样性。结果 在健康人,巨单胞菌属、拟杆菌属和粪杆菌属分别为14.8%、11.4%和9.8%,在代偿期肝硬化组,拟杆菌属、粪杆菌属和巨单胞菌属比例分别为15.2%、11.5%和11.2%,在失代偿期肝硬化组,拟杆菌属、粪杆菌属和韦荣球菌属比例分别为16.9%、9.6%和9.2%;健康人Chao指数为(1250.5±283.7),显著高于代偿期肝硬化组【(1111.5±277.1),P＜0.05】或失代偿期肝硬化组【(910.2±369.6),P＜0.05】,健康人Shannon指数为(3.7±0.6),显著高于代偿期肝硬化组【(3.5±0.1),P＜0.05】或失代偿期肝硬化组【(3.3±0.4),P＜0.05】,健康人Simpson指数为(0.3±0.1),显著高于代偿期肝硬化组【(0.2±0.1),P＜0.05】或失代偿期肝硬化组【(0.1±0.4),P＜0.05】。结论 乙型肝炎肝硬化患者肠道菌群丰度和多样性降低,失代偿期肝硬化患者肠道菌群变化更为明显,即存在随着病情进展肠道菌群多样性减少现象,其临床意义值得探讨。