肠道菌群改变对非酒精性脂肪性肝病的影响

目的研究非酒精性脂肪性肝病（NAFLD）患者的肠道菌群变化,以及微生态制剂对其影响。方法60例N A FLD患者,以60例健康体检者作对照,采集粪便标本,测定肠道菌群。N A FLD患者给予枯草杆菌二联活菌肠溶胶囊口服（500 mg/次,3次/d）,疗程3个月,观察治疗前后肝功能（ALT、AST、GGT ）及血脂（TC、TG）水平的变化,肝脏脂肪定量及粪便中肠道菌群变化。结果 NAFLD组治疗前肠道葡萄球菌较健康对照组显著增多,双歧杆菌、乳杆菌、肠球菌数量明显降低（P＜0．05）;NAFLD患者治疗后与治疗前相比,肝功能（ALT、AST ）、血脂（TC）水平明显下降、肝脏脂肪定量明显减少,肠球菌、双歧杆菌及乳杆菌数量明显上升,葡萄球菌数量明显下降（P＜0．05）。结论 NAFLD患者存在肠道菌群改变,微生态制剂在N A FLD治疗中有重要的临床意义。     

饮食干预对非酒精性脂肪性肝病肠道菌群的影响

非酒精性脂肪性肝病(NAFLD)的发生与遗传和环境密切相关,肠道菌群在其发生和发展中发挥了重要作用,调节肠道菌群已成为干预NAFLD的重要靶点之一.无论是饮食总量还是结构都会对肠道菌群产生直接且长期的影响.通过低脂饮食、增加饮食中不饱和脂肪酸或者增加难以吸收的多糖等方式调整饮食结构,可以有效调节肠道菌群并治疗NAFLD,但高蛋白饮食的作用还存在争议.     

肠道菌群与非酒精性脂肪性肝病

非酒精性脂肪性肝病（NAFLD）是一种常见慢性肝病,发病率呈逐年升高趋势,已逐渐引起人们的重视。1998年马歇尔正式提出了“肠-肝轴”的概念,肠道内环境与肝脏关系密切,越来越多的证据表明肠道菌群失调在NAFLD发病机制中起到了重要的作用。本文介绍了肠道菌群与NAFLD发病机制的关系。     

肠道菌群对非酒精性脂肪性肝病铁代谢的影响

<正>非酒精性脂肪性肝病(NAFLD)是与胰岛素抵抗(IR)及遗传易感性密切相关的一组以肝脏脂质过度蓄积为主要病理表现的慢性代谢性肝脏疾病^[1]。其主要包括：单纯性脂肪肝、非酒精性脂肪性肝炎(NASH)、NASH相关性肝硬化。预计到2030年中国的NAFLD总人数将增加到3.145 8亿例,是全球NAFLD患病率增长最快的国家^[2]。然而,关于NAFLD的发病机制目前尚未完全阐明。“多重打击学说”是当前研究最多的NAFLD的发病机制,     

酪酸梭菌对非酒精性脂肪性肝病患者肠道菌群的影响研究

目的 通过比较酪酸梭菌用药前后NAFLD患者的生化指标、B超结果及肠道菌群构成等,评价酪酸梭菌对NAFLD的疗效及对肠道菌群的影响。方法 选择在我院消化内科就诊的NAFLD患者100例,另选50名健康对照者,分别用16S rDNA高通量测序检测两组的肠道菌群含量。所有NAFLD患者随机分为两组,对照组予以低脂饮食+有氧运动(如存在转氨酶升高,予以双环醇1粒tid po),观察组在此基础上联用酪酸梭菌(2粒tid po),3个月后通过Illumina NovaSeq平台对样本粪便DNA进行测序,观察肠道菌群变化,同时复查腹部B超、血脂(TG、CHOL)、肝功能(ALT、AST)、炎症因子(IL-6、TNF-α)、肠屏障指标(血清内毒素、DAO、D-乳酸活性水平)等。结果 NAFLD患者较健康人群的厚壁菌减少,肠杆菌增多;肠屏障指标血清内毒素、DAO、D-乳酸活性水平升高。用药后观察组肠道有益菌较治疗前增多。两组的内毒素、DAO、D-乳酸水平均较治疗前下降(P<0.05),观察组下降较对照组更明显,差异有统计学意义(P<0.05)。观察组的治疗有效率(86.0%)高于对照组(7...     

非诺贝特对非酒精性脂肪性肝病小鼠模型肠道菌群多样性的影响

目的探讨非诺贝特对非酒精性脂肪性肝病(NAFLD)小鼠肠道菌群多样性的影响。方法将30只小鼠随机分为3组,正常组(n=10)、高脂组(n=10)、非诺贝特治疗组(n=10),高脂组与非诺贝特治疗组给予高脂饮食干预14周,正常组给予普通饮食14周。在满10周开始对非诺贝特治疗组给予非诺贝特灌胃治疗并继续给予高脂饮食4周,全程监测小鼠体质量变化; 14周后收集3组粪便用于高通量测序16S rRNA分析菌群的多样性及差异;并收集肝组织进行HE染色及油红O染色观察脂肪变性情况。多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果干预10周后,非诺贝特治疗组较高脂组体质量明显减轻(P 0. 05)。HE染色及油红O染色显示非诺贝特治疗组脂肪沉积较高脂组明显减少。非诺贝特治疗组与高脂组肠道菌群存在明显差异,而与正常组肠道菌群具有相似性,非诺贝特治疗组拟杆菌门、疣微菌门、Faecalibaculum、Muribaculaceae_norank、阿克曼菌属丰度明显升高,厚壁菌门、放线菌门、梭菌属、Turicibacter、双歧杆菌属丰度降低。结论拟杆菌门、疣微菌门丰度明显升高,厚壁菌门、放线菌门丰度降低在非诺贝特治疗NAFLD中可能存在积极意义。     

非酒精性脂肪性肝病与肠道菌群失调新观点

非酒精性脂肪性肝病（NAFLD）在世界范围内患病率逐渐升高,“二次打击学说”发病机制已经被认可,但是具体的病理生理学发病机制还不完全清楚。近期,已有大量研究的新观点来解释肠道菌群在 NAFLD 发病机制中的作用,包括调节肠粘膜通透性、低水平炎症反应和免疫平衡,调节饮食胆碱代谢,调节胆汁酸代谢和增加细菌产生的内源性乙醇等。这些因素在分子水平上解释了肠道菌群如何促发 NAFLD 的发生,并进一步诱导其向非酒精性脂肪性肝炎（NASH）进展。     

饮食对非酒精性脂肪性肝病肠道微生物菌型相关菌群的影响

非酒精性脂肪性肝病(NAFLD)是一种典型的慢性肝病,与肠道微生态的失调密切相关。饮食因素可能是影响肠道细菌组成和功能的最重要的驱动因素。基于肠道微生物菌型的概念,总结了饮食对NAFLD肠道微生物菌型相关菌群的影响,包含厚壁菌门/拟杆菌门的比值、拟杆菌属、普雷沃菌属、瘤胃球菌属、变形菌门、放线菌门及其他菌。指出改善饮食进而调节肠道菌群是防治NAFLD的重要策略之一,具有良好的前景,但尚需进一步的机制和临床研究。     

非酒精性脂肪性肝病与肠道菌群的关系

非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)是一种多病因导致的临床病理综合征,已成为最常见的慢性肝病之一,目前NAFLD完整的生理机制尚不完全清楚,近年来提出肠道菌群通过调控能量代谢、增加内源性乙醇、调节胆汁酸及胆碱代谢,破坏免疫平衡引发机体低度炎症等途径促进NAFLD的发生、发展,本文就肠道菌群与NAFLD的相关机制做一概述。     

非酒精性脂肪性肝病对肠道炎症及通透性的影响

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大鼠是否也同时伴随存在肠道炎症,并探讨NAFLD对肠道通透性的影响。方法 24只雄性大鼠以1∶1比例随机接受标准饲料和高脂饲料喂食18周,分别建立对照组和NAFLD大鼠模型。通过大鼠肝脏病理切片HE染色和油红O染色验证模型的成立,根据大鼠结肠病理切片HE染色观察是否存在肠道炎症进行进一步分组分析。使用酶联免疫吸附测定血浆二胺氧化酶、D-乳酸水平和内毒素水平,检测肠道通透性改变情况。结果与对照组相比,12只NAFLD大鼠肝脏均呈大泡和小泡性脂肪变以及气球样变,其中发现有7只大鼠的肠道存在轻度炎症细胞浸润,组织学符合肠道炎症改变;NAFLD组中另5只大鼠未见组织学上肠道炎症改变;而在对照组中未见任何肠道炎症改变。与对照组相比,NAFLD大鼠血浆中二胺氧化酶和D-乳酸水平显著升高(P0.05)。其中,NAFLD伴肠道炎症组大鼠的D-乳酸水平较NAFLD不伴肠道炎症组显著升高(P0.05)。NAFLD伴肠道炎症组大鼠血浆中LBP水平明显高于对照组和NAFLD不伴肠道炎症组(均P0.05)。结论 NAFLD可增加肠道炎症发生的风险,NAFLD导致肠道炎症时肠道通透性显著增加。     

Treatment of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the most common cause for elevated liver enzymes in the developed nations. Beyond prevention programs which are of particular interest because of the increasing number of overweight children, treatment should be focussed on the most important risk factors, obesity and insulin resistance. As a consequence of elucidating the pathomechanisms of NAFLD, the number of potential therapeutic options increased. However, many studies investigating the therapeutic effect show shortcomings in at least one of the following points: lack of a serial liver biopsy, short term of treatment and limited number of included patients. The second generation insulin sensitizer piogiitazone and rosiglitazone show the most promising improvements in NAFLD, but weight gain and potential hepatotoxicity calls for attention. In conclusion, a general recommendation for the application of specific drugs cannot be given. Besides controlled clinical trials, weight reduction and physical activity to improve insulin sensitivity in obese patients should be the priority objective.     

Probiotics as a complementary therapeutic approach in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is currently recognized as one of the most common causes of chronic liver disease. It involves a spectrum of conditionsthat include pure steatosis without inflammation, steatohepatitis, fibrosis and cirrhosis. The key factor in the pathophysiology of NAFLD is insulin resistance that determines lipid accumulation in the hepatocytes and, thus, oxidative stress, which is followed by inflammatory response. However, NAFLD pathogenesis is still largely unknown and has been extensively investigated. Although life style modification with the aim of losing weight has been advocated to treat this disorder, its effectiveness is limited; additionally, there is no specific pharmacologic treatment until nowadays. Recent evidence suggests that the gut microbiota may play a role in the development of insulin resistance, hepatic steatosis, necroinflammation and fibrosis. Differences in gut microbiota between NAFLD patients and lean individuals as well as presence of small intestinal bacterial overgrowth in NAFLD subjects have been demonstrated. Furthermore, some data indicate that the immunoregulatory effects of probiotics may be beneficial in NAFLD treatment as they modulate the intestinal microbiota; improve epithelial barrier function and strengthen the intestinal wall decreasing its permeability; reduce bacterial translocation and endotoxemia; improve intestinal inflammation; and reduce oxidative and inflammatory liver damage. In this article, we review the clinical trials on the use of probiotics in the treatment of NAFLD and discuss the effects of these agents and their efficacy as an emerging therapeutic resource to treat NAFLD patients.     

Histopathology of nonalcoholic fatty liver disease

Histological analysis of liver biopsies remains a standard against which other methods of assessment for the presence and amount of hepatic injury due to nonalcoholic fatty liver disease(NAFLD) are measured.Histological evaluation remains the sole method of distinguishing steatosis from advanced forms of NAFLD,i.e.nonalcoholic steatohepatitis(NASH) and fibrosis.Included in the lesions of NAFLD are steatosis,lobular and portal inflammation,hepatocyte injury in the forms of ballooning and apoptosis,and fibros...     

Increased circulating zonulin in children with biopsy-proven nonalcoholic fatty liver disease

AIM:To investigate the potential association of circulating zonulin with the stage of liver disease in obese children with biopsy-confirmed nonalcoholic fatty liver disease(NAFLD).METHODS:A case-control study was performed.Cases were 40 obese children with NAFLD.The diagnosis of NAFLD was based on magnetic resonance imaging(MRI)with high hepatic fat fraction(HFF≥5%),and confirmed by liver biopsy with≥5%of hepatocytes containing macrovesicular fat.Controls were selected from obese children with normal levels of aminotransferases,and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases.Controls were matched(1-to 1)with the cases on age,gender,pubertal stage and as closely as possible on body mass index-standard deviation score.All participants underwent clinical examination,laboratory testsincluding zonulin,inflammatory and metabolic parameters,and MRI for measurement of HFF and visceral adipose tissue.RESULTS:Zonulin values were significantly greater in obese subjects with NAFLD than in those without NAFLD[median(interquartile range),4.23(3.18-5.89)vs 3.31(2.05-4.63),P<0.01].In patients with NAFLD,zonulin concentrations increased significantly with the severity of steatosis and the Spearman’s coefficient revealed a positive correlation between zonulin values and steatosis(r=0.372,P<0.05);however,we did not find a significant correlation between zonulin and lobular inflammation(P=0.23),ballooning(P=0.10),fibrosis score(P=0.18),or presence of nonalcoholic steatohepatitis(P=0.17).Within the entire study population,zonulin levels were positively associated with gamma-glutamyl transferase,2-h insulin,HFF,and negatively associated with whole-body insulin sensitivity index(WBISI),after adjustment for age,gender and pubertal status.When the associations were restricted to the group of NAFLD patients,2-h insulin,hepatic fat,and WBISI retained statistical significance.CONCLUSION:Circulating zonulin is increased in children and adolescents with NAFLD and correlates with the severity of steatosis.     

肠道益生菌对非酒精性脂肪肝的影响

目的探讨肠道菌群与非酒精性脂肪肝(NAFLD)的关系。方法对53例服用肠道益生菌的NAFLD患者和56例对照组患者进行服药前后肝脏的超声检查,抽血查血肌酐、尿素氮、总胆固醇、三酰甘油、空腹血糖,并同时对年龄和体质量指数(BMI)进行统计。结果服药前两组各项指标比较,差异无统计学意义(P0.05)。服药后肠道益生菌组和对照组比较,脂肪肝消退数明显增加,差异有统计学意义(P0.05)。服药前后两组比较,肠道益生菌组服药后较服药前脂肪肝消退数明显增加,差异有统计学意义(P0.01);而对照组各项指标比较,差异均无统计学意义(P0.05)。两组服药前后各种观察指标差值的比较,脂肪肝消退、中度脂肪肝减少数、总胆固醇、三酰甘油和尿素氮下降在肠道益生菌组差异有统计学意义(P0.05、P0.01)。结论口服益生菌可以降低NAFLD的发生,益生菌可能具有预防和治疗NAFLD的作用。     

Obesity,fatty liver disease and intestinal microbiota

Nonalcoholic fatty liver disease(NAFLD) is a chronic liver disorder that is increasing in prevalence with the worldwide epidemic of obesity. NAFLD is the hepatic manifestation of the metabolic syndrome. The term NAFLD describes a spectrum of liver pathology ranges from simple steatosis to steatosis with inflammation nonalcoholic steatohepatitis and even cirrhosis. Metabolic syndrome and NAFLD also predict hepatocellular carcinoma. Many genetic and environmental factors have been suggested to contribute to the development of obesity and NAFLD, but the exact mechanisms are not known. Intestinal ecosystem contains trillions of microorganisms including bacteria, Archaea, yeasts and viruses. Several studies support the relationship between the intestinal microbial changes and obesity and also its complications, including insulin resistance and NAFLD. Given that the gut and liver are connected by the portal venous system, it makes the liver more vulnerable to translocation of bacteria, bacterial products, endotoxins or secreted cytokines. Altered intestinal microbiota(dysbiosis) may stimulate hepatic fat deposition through several mechanisms: regulation of gut permeability, increasing low-grade inflammation, modulation of dietary choline metabolism, regulation of bile acid metabolism and producing endogenous ethanol. Regulation of intestinal microbial ecosystem by diet modifications or by using probiotics and prebiotics as a treatment for obesity and its complications might be the issue of further investigations.     

Transition of an acronym from nonalcoholic fatty liver disease to metabolic dysfunction-associated fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is a global public health concern owing to its substantial contribution to chronic liver diseases. The disease is closely linked to metabolic syndrome(MS), suggesting a common biological pathway and shared disease mechanism for both ailments. Previous studies revealed a close relationship of NAFLD with the components of MS including abdominal obesity,dyslipidemia, hypertension, and hyperglycemia. Hence, a group of experts recently renamed NAFLD as metabolic dysfunction-associated fatty liver disease(MAFLD) in order to encompass a more appropriate pathogenesis of the disease.NAFLD was first named to describe a condition similar to alcoholic hepatitis in absence of significant alcohol consumption. However, knowledge pertaining to the etiopathogenesis of the disease has evolved over the past four decades. Recent evidence endorses NAFLD as a terminology of exclusion and suggests that it may often leads to misdiagnosis or inappropriate management of patients, particularly in clinical practice. On the other hand, the new definition is useful in addressing hepatic steatosis with metabolic dysfunction, which ultimately covers most of the patients with such illness. Therefore, it seems to be helpful in improving clinical diagnosis and managing high-risk patients with fatty liver disease. However, it is imperative to validate the new terminology at the population level to ensure a holistic approach to reduce the global burden of this heterogeneous disease condition.     

非酒精性脂肪性肝病的相关危险因素研究进展

非酒精性脂肪性肝病(NAFLD)是指一群组织病理异常,其发病以胰岛素抵抗为基础,并与肥胖、高脂血症、Ⅱ型糖尿病、原发性高血压等密切相关。疾病早期症状隐匿,如不及时控制可诱发肝硬化及慢性肝病。NAFLD治疗策略有限,因此探讨脂肪肝相关危险因素对降低NAFLD发病及延缓其病程进展具有重要意义。