非酒精性脂肪性肝病与肠道微生态

<正>随着肥胖和代谢综合征(MS)的流行,非酒精性脂肪性肝病(NAFLD)的发病率逐渐上升,已成为我国最常见的慢性肝病^[1]。NAFLD发病机制是基于“二次打击”假说而提出的“多重打击”假说^[2]。近些年,有新的观点认为肠道菌群(intestinal microecology,IM)与NAFLD密切相关。在动物模型研究发现,肠道微生态失衡可以导致肝脏脂肪变性、炎症、甚至肝纤维化等。根据肠-肝轴理论,肠道微生态平衡被破坏时,有害的肠道细菌及其代谢产物能够通过门脉系统进入肝脏,造成机体免疫应答和炎症反应,进而导致NAFLD的发生和发展^[3]。     

肠道微生态失衡与非酒精性脂肪性肝病的关系

肠道微生态系统由定植于肠道的固有菌群、肠上皮细胞、肠黏膜免疫系统组成。非酒精性脂肪性肝病(NAFLD)是一种与胰岛素抵抗和遗传易感性相关的代谢应激性肝损伤。近年来关于肠道微生态与NAFLD发病机制关系的研究越来越多。肠道微生态失衡导致的肠道菌群过度生长、肠黏膜通透性增加、肠源性内毒素血症、炎症因子产生等在NAFLD的发生发展过程中扮演着重要的角色。深入研究肠道微生态失衡与NAFLD的关系将有助于为NAFLD的治疗及预防提供新方向。     

肠道微生态与非酒精性脂肪性肝病关系的研究进展

非酒精性脂肪性肝病(NAFLD)是一种与胰岛素抵抗和遗传易感性密切相关,以肝实质细胞脂肪变性和脂质沉积为特征的临床病理综合征。近年来研究发现,肠道微生态失衡通过干扰宿主物质代谢、促进胰岛素抵抗、破坏肠道免疫功能,在NAFLD的发生发展中起重要作用。采用微生态制剂调节和重建肠道微生态也成为NAFLD防治的热点。此文就肠道微生态与NAFLD关系的研究进展作一综述。     

肠道微生态在非酒精性脂肪性肝病发病机制中的研究进展

NAFLD已成为当今发达国家和中国富裕地区慢性肝病的首要病因。近年来研究显示,肠道微生态失衡在NAFLD发病中起重要作用。肠道微生态构成和功能改变可以通过影响能量吸收和储存、产生肥胖、促进胰岛素抵抗、胆碱缺乏、干扰胆汁代谢、产生内源性乙醇等机制影响物质代谢,通过SIBO改变小肠动力及促进炎症因子吸收,这些均与NAFLD发生或从单纯脂肪性肝病进展至NASH有关。肠黏膜通透性改变、肠源性内毒素血症、肝细胞或Kupffer细胞激活及促炎因子生成在NAFLD及NASH的发生中起到核心作用。NAFLD进展到一定阶段后．又会反过来影响肠道微牛态的平衡．最终两者形成恶件循环．     

肠道菌群代谢产物在非酒精性脂肪性肝病发病中的作用机制研究进展

非酒精性脂肪性肝病（NAFLD）是一种代谢相关的慢性肝脏疾病，主要病因为肝脏内脂质堆积过多，可逐渐发展为肝纤维化、肝硬化甚至肝癌。肠道菌群是人体内微生物群的重要组成部分，可通过肠肝轴（GLA）参与NAFLD的发病过程，其分泌的代谢产物短链脂肪酸、胆汁酸、细菌成分、内源性乙醇及胆碱在NAFLD发病过程中均发挥重要作用。肠道菌群代谢产物与NAFLD的发病机制存在密切关联，深入了解其作用机制，或可为通过肠道微生态预防及治疗NAFLD提供理论依据。     

非酒精性脂肪性肝病与结直肠肿瘤相关性机制的研究进展

随着人们生活方式及饮食结构的改变,非酒精性脂肪性肝病(NAFLD)的发病率逐年升高,已成为较常见的慢性肝脏疾病。近年来多项研究提示,NAFLD能够增加结直肠肿瘤(包括结直肠腺瘤和结直肠癌)的发病风险。多种机制如胰岛素抵抗、脂质代谢异常、炎性反应和氧化应激以及肠道微生态等与NAFLD患者结直肠肿瘤的发病有关。     

肠道微生态失衡与非酒精性脂肪性肝病

近年来,有关肠道微生态与人类疾病（包括代谢性疾病、胃肠道疾病以及肝病等）关系的研究越来越多。相关临床和动物实验研究已证实,肠道微生物通过肝肠轴参与非酒精性脂肪性肝病（NAFLD）的发生发展［1］。为此,我们就肠道微生态失衡对 NAFLD 影响的最新进展综述如下。     

肠道微生态变化与非酒精性脂肪性肝病研究进展

由定植于肠道的大量固有菌群、肠道上皮细胞及肠道局部粘膜免疫系统组成了肠道微生态系统。"肝-肠轴"概念的提出为从肠道微生态角度寻找非酒精性脂肪性肝病(NAFLD)的诊疗措施提供了依据。肠道微生态失衡所致的肠道菌群过度生长、肠黏膜通透性改变、免疫功能紊乱、肠源性内毒素血症、效应细胞激活及炎症因子生成等在NAFLD发生发展中发挥了不容忽视的作用。深入研究肠道菌群与NAFLD之间的关系将为NAFLD的预防和治疗提供新靶点。     

肠道菌群与非酒精性脂肪肝关系的研究进展

<正>非酒精性脂肪肝(NAFLD)是代谢综合征的肝脏表现,是全球最常见的慢性肝病。肠道菌群在NAFLD发病机制中发挥重要作用。肠道菌群可通过影响能量代谢、诱导内毒素血症、产生内源性乙醇、调节胆汁酸和胆碱代谢等多种机制促进NAFLD的发病。益生菌和益生元等肠道菌群靶向治疗在许多动物研究中已获得积极的疗效。本研究对肠道菌群与NAFLD关系的研究进展进行综述。1 NAFLD概述NAFLD是指排除过量饮酒、病毒感染或其他肝脏疾病,以肝脏脂肪异     

肠道微生态失调与非酒精性脂肪性肝病关系研究进展

非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)俗称脂肪肝,临床常见,患病率持续上升,发病机制未完全明确,尚无有效防治方法.近年,随着高通量测序的应用,胃肠道微生态研究取得进展,已证实微生态失调(包括胃肠道菌群改变,细菌移位和小肠细菌过度生长等)和NAFLD发病相关,肠道微生态失调除了破坏肠黏膜屏障外,更主要是通过"肠-肝轴"令细菌及其毒性产物进入肝脏,经Toll样受体和NOD样受体通路激活肝脏免疫系统,炎症因子(如肿瘤坏死因子、白介素等)诱发肝脏炎症,导致,NAFLD.应用微生态制剂、抗生素及粪菌移-植等方法取得一定疗效,为NAFLD防治开辟,新的途径.     

粪菌移植治疗非酒精性脂肪性肝病研究进展

非酒精性脂肪肝病（non-alcoholic fatty liver disease, NAFLD）的发病率在世界范围内呈明显上升趋势,由于目前尚无确切的特效治疗方式,严重影响人类健康。近年来,越来越多的研究表明肠道菌群通过肝-肠轴影响肝功能,肠道菌群失调是NAFLD发病的重要原因。因此,纠正肠道菌群失调,可以预防和减轻NAFLD的发生、发展。粪菌移植（fecal microbiota transplantation, FMT）被认为是纠正肠道菌群失调最有效的方法,但其在NAFLD中的治疗作用还未明确。此外,FMT治疗NAFLD的潜在分子机制也尚未阐明。本文就FMT治疗NAFLD的研究现状进行总结,并发掘其潜在的分子机制,为FMT作为治疗NAFLD的有效手段提供理论支持。     

非酒精性脂肪性肝病代谢组学研究进展

非酒精性脂肪性肝病(NAFLD)发病率逐渐升高,已成为我国第一大慢性肝病的首要原因。目前对NAFLD的发病机制并未完全阐明且无特效药物。从发病机制、无创诊断、药物作用与疗效角度出发,介绍了以机体内源性小分子代谢物为研究对象的代谢组学在NAFLD中的研究进展,为进一步探索NAFLD提供新的思路与方法。     

肠道微生态与肝癌关系研究新进展

由于肝脏与肠道紧密的解剖与功能关系,肠道微生物通过肝-肠循环和微生态-肝脏轴与宿主相互作用,在肝脏炎症、慢性纤维化及肿瘤发生发展中发挥重要作用。肠道微生态失衡促进肝癌进展,这是国际上实验动物肝癌发病机制的突破性进展。肠道微生物中关键功能菌可能成为肝癌诊治的新型生物标志物和治疗靶点。随着第二代高通量测序技术的发展,元基因组学研究从极大的深度和广度为我们认识肠道菌群与肝癌的关系开辟了新的途径。     

非酒精性脂肪性肝病动物实验模型研究进展

近年来随着肥胖、2型糖尿病、高脂血症等发生率的升高,非酒精性脂肪性肝病(NAFLD)的发病率也逐渐升高,成为常见的慢性肝脏疾病之一,而在我国是仅次于慢性病毒性肝炎的第二大肝病。但其发病机制仍未阐明,因NAFLD的发生和演进病程长,且从人体获取肝组织进行研究或药物试验等受伦理限制,因此NAFLD动物模型在本病研究中起了重要作用。综述了具备与NAFLD患者组织病理学表现相似的动物模型,并比较其建模原理及优缺点。为深入研究NAFLD发病机制,筛选防治药物等提供了有利工具。     

Mitochondrial carnitine palmitoyltransferase-Ⅱ dysfunction:A possible novel mechanism for nonalcoholic fatty liver disease in hepatocarcinogenesis

Nonalcoholic fatty liver disease(NAFLD) or metabolic-associated fatty liver disease has been characterized by the lipid accumulation with injury of hepatocytes and has become one of the most common chronic liver diseases in the world.The complex mechanisms of NAFLD formation are still under identification.Carnitine palmitoyltransferase-Ⅱ(CPT-Ⅱ) on inner mitochondrial membrane(IMM) regulates long chain fatty acid β-oxidation,and its abnormality has had more and more attention paid to it by basic ...     

What does irritable bowel syndrome share with non-alcoholic fatty liver disease?

Non-alcoholic fatty liver disease(NAFLD)and irritable bowel syndrome(IBS)are two very common diseases in the general population.To date,there are no studies that highlight a direct link between NAFLD and IBS,but some recent reports have found an interesting correlation between obesity and IBS.A systematic PubMed database search was conducted highlighting that common mechanisms are involved in many of the local and systemic manifestations of NAFLD,leading to an increased cardiovascular risk,and IBS,leading to microbial dysbiosis,impaired intestinal barrier and altered intestinal motility.It is not known when considering local and systemic inflammation/immune system activation,which one has greater importance in NAFLD and IBS pathogenesis.Also,the nervous system is implicated.In fact,inflammation participates in the development of mood disorders,such as anxiety and depression,characteristics of obesity and consequently of NAFLD and,on the other hand,in intestinal hypersensitivity and dysmotility.     

Intestinal microbiome and NAFLD: molecular insights and therapeutic perspectives

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of dysregulated lipid and glucose metabolism, which is often associated with obesity, dyslipidemia and insulin resistance. In view of the high morbidity and health risks of NAFLD, the lack of effective cure has drawn great attention. In recent years, a line of evidence has suggested a close linkage between the intestine and liver diseases such as NAFLD. We summarized the composition and characteristics of intestinal microbes and reviewed molecular insights into the intestinal microbiome in development and progression of NAFLD. Intestinal microbes mainly include bacteria, archaea, viruses and fungi, and the crosstalk between non-bacterial intestinal microbes and human liver diseases should be paid more attention. Intestinal microbiota imbalance may not only increase the intestinal permeability to gut microbes but also lead to liver exposure to harmful substances that promote hepatic lipogenesis and fibrosis. Furthermore, we focused on reviewing the latest “gut–liver axis”-targeting treatment, including the application of antibiotics, probiotics, prebiotics, synbiotics, farnesoid X receptor agonists, bile acid sequestrants, gut-derived hormones, adsorbents and fecal microbiota transplantation for NAFLD. In this review, we also discussed the potential mechanisms of “gut–liver axis” manipulation and efficacy of these therapeutic strategies for NAFLD treatment.

     

Non-alcoholic fatty liver disease,obesity and the metabolic syndrome

Nonalcoholic fatty liver disease (NAFLD) is now recognized as the most common cause of chronic liver disease worldwide. Its prevalence has increased to more than 30% of adults in developed countries and its incidence is still rising. The majority of patients with NAFLD have simple steatosis but in up to one third of patients, NAFLD progresses to its more severe form nonalcoholic steatohepatitis (NASH). NASH is characterized by liver inflammation and injury thereby determining the risk to develop liver fibrosis and cancer. NAFLD is considered the hepatic manifestation of the metabolic syndrome. However, the liver is not only a passive target but affects the pathogenesis of the metabolic syndrome and its complications. Conversely, pathophysiological changes in other organs such as in the adipose tissue, the intestinal barrier or the immune system have been identified as triggers and promoters of NAFLD progression. This article details the pathogenesis of NAFLD along with the current state of its diagnosis and treatment.     

Probiotics in non-alcoholic fatty liver disease: which and when

Non-alcoholic fatty liver disease (NAFLD) is a common and serious disease. Literature reports the central role of the gut-liver axis in the pathogenesis of NAFLD, and recently suggests that the microbiota is a casual factor of the disease, involved in the interactions between intestinal lumen and liver. Probiotic are commensal bacteria, able to modulate the microbiota with benefits for the health of humans. Several data suggest a range of potentially beneficial medicinal uses for probiotics, in particular in NAFLD patients. However, the species with higher efficacy in this disease are not identified. The present review focuses on the role of gut-liver axis in the pathogenesis, and on the potential therapeutic role of probiotics in the managing of NAFLD.