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。     

肠道菌群代谢产物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)是一种常见的慢性肝脏疾病,其发病率呈逐年上升趋势。NAFLD的发病机制尚未完全阐明,目前研究显示肠道菌群分泌的代谢产物在NAFLD的发生发展过程中起着重要作用,包括调节能量平衡,作为信号分子参与信号转导,直接作用于肝脏细胞等。该文对近年来肠道菌群代谢产物(如短链脂肪酸、氧化三甲胺、胆汁酸及内生性乙醇等)与NAFLD关系的相关研究作一综述,并探讨基于肠道菌群代谢产物的NAFLD防治策略。     

基于肠-肝轴理论探讨非酒精性脂肪性肝病和肠道菌群的关系

非酒精性脂肪性肝病(NAFLD)目前已成为最主要的慢性肝病,被认为是代谢综合征的肝脏表现,后期可能向肝纤维化及肝硬化,甚至是肝癌发展。肠道菌群作为人体重要的共生物,影响人体的代谢功能,可能和NAFLD的发病密切相关。肠-肝轴理论为"肠道菌群失调可引起肝脏改变"提供了理论基础。探讨了肠道菌群和NAFLD发病的关系,为后期研究肠道菌群靶向治疗NAFLD奠定理论基础。     

肠道微生态失衡致非酒精性脂肪性肝病发病机制的研究进展

非酒精性脂肪性肝病（NAFLD）已成为一种常见的慢性肝病。近年肠道微生态失衡致NAFLD发病的机制研究已成为一个新的热点。国内外文献已报道相关发病机制可能包括干扰代谢、促进胰岛素抵抗、产生毒性代谢产物、增加肠壁通透性、激活肠道免疫、加重肝脏脂质氧化和氧化应激、激活肝脏免疫炎症损伤和肝纤维化等。而NAFLD发展到一定阶段后又可反过来影响肠道微生态,形成恶性循环。本文就肠道微生态失衡致NAFLD发病机制的研究进展作一综述。     

短链脂肪酸在非酒精性脂肪性肝病发生发展中作用的研究进展

非酒精性脂肪性肝病(NAFLD)是一种常见的、多因素导致的肝病,有进展为非酒精性脂肪性肝炎(NASH)、肝硬化甚至肝细胞癌的风险,其发病机制尚不明确。短链脂肪酸(SCFA)是肠道菌群的重要代谢产物之一。近年来多项研究指出,SCFA在NAFLD的发生发展中发挥了巨大作用,其机制可能与保护肠道屏障、改善葡萄糖和脂代谢、调节免疫应答等途径有关。此文主要探讨SCFA在肠道稳态、代谢、免疫应答以及肠道动力学等方面的研究进展,并阐述其在NAFLD发生发展中的可能作用。     

丁酸在非酒精性脂肪性肝病预防和治疗中作用的研究进展

非酒精性脂肪性肝病(NAFLD)是全世界最常见的慢性肝病,其发病率呈逐年上升趋势。NAFLD发病的分子机制尚不完全清楚,临床缺乏有效的防治手段。近年研究发现,丁酸作为一种短链脂肪酸(SCFAs)在基因调控、免疫调节、肿瘤抑制、肠道黏膜屏障调节、氧化应激减轻等方面发挥重要作用。已有多项研究表明丁酸可缓解NAFLD,本文就丁酸参与NAFLD发病的主要机制及其在NAFLD治疗方面的应用作一综述,以期能为NAFLD的防治提供新思路。     

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。     

肠道菌群和内毒素血症与非酒精性脂肪性肝病

＂肝-肠轴＂概念的提出为寻找肝病的发病机制和诊疗方法提供了新思路。大量研究发现,肠道菌群数量和结构改变通过影响能量吸收、促进肥胖、参与胰岛素抵抗、导致小肠细菌过度生长和内毒素血症等机制促进非酒精性脂肪性肝病（NAFLD）的发生和发展;抗生素或益生菌可通过调节肠道菌群、恢复肠道微生态平衡等作用有可能能防治NAFLD等代谢性疾病。     

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。     

非酒精性脂肪性肝病与抑郁症的关系

非酒精性脂肪性肝病(NAFLD)已成为世界上最常见的慢性肝病之一。随着生物-心理-社会医学模式的发展,NAFLD患者的精神健康问题逐渐受到重视。近年来,NAFLD与精神性疾病,特别是抑郁症的相关研究越来越多,且证实二者存在明显的相关性。但二者相关性的共同病理生理机制仍不明确,孰因孰果及治疗方式亟待进一步研究。综述了NAFLD与抑郁症的关系、共同病理生理机制及治疗的研究进展。期望为两者关系更深层次的研究打下基础,有助于未来临床对这两种疾病进行联合预防和治疗。     

Microbiota and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH)

Genetic predisposition, the intestinal microbiota (IM) and environmental factors, such as sedentary lifestyle and inadequate diet, should be considered as critical factors for the development of nonalcoholic fatty liver disease (NAFLD). Recently, some studies have demonstrated an association between dysbiosis and NAFLD; however, the exact mechanisms that lead to intestinal membrane damage, bacterial translocation and inflammation are not well elucidated. Due to the relevance of this theme, the IM and its metabolites have received special attention in recent years in an attempt to better understand the mechanisms related to the prevention, physiopathology, and treatment of NAFLD. In this paper, we provide a review of the human IM and its role in diet, obesity, and the development/progression of NAFLD/NASH, as well as the use of prebiotics and probiotics in the modulation of IM.     

G protein-coupled receptors as potential targets for nonalcoholic fatty liver disease treatment

Nonalcoholic fatty liver disease(NAFLD)is a broad-spectrum disease,ranging from simple hepatic steatosis to nonalcoholic steatohepatitis,which can progress to cirrhosis and liver cancer.Abnormal hepatic lipid accumulation is the major manifestation of this disease,and lipotoxicity promotes NAFLD progression.In addition,intermediate metabolites such as succinate can stimulate the activation of hepatic stellate cells to produce extracellular matrix proteins,resulting in progression of NAFLD to fibrosis and even cirrhosis.G protein-coupled receptors(GPCRs)have been shown to play essential roles in metabolic disorders,such as NAFLD and obesity,through their function as receptors for bile acids and free fatty acids.In addition,GPCRs link gut microbiota-mediated connections in a variety of diseases,such as intestinal diseases,hepatic steatosis,diabetes,and cardiovascular diseases.The latest findings show that gut microbiota-derived acetate contributes to liver lipogenesis by converting dietary fructose into hepatic acetyl-CoA and fatty acids.GPCR agonists,including peptides and natural products like docosahexaenoic acid,have been applied to investigate their role in liver diseases.Therapies such as probiotics and GPCR agonists may be applied to modulate GPCR function to ameliorate liver metabolism syndrome.This review summarizes the current findings regarding the role of GPCRs in the development and progression of NAFLD and describes some preclinical and clinical studies of GPCR-mediated treatment.Overall,understanding GPCR-mediated signaling in liver disease may provide new therapeutic options for NAFLD.     

非酒精性脂肪性肝病发生及进展的危险因素

非酒精性脂肪性肝病(NAFLD)的患病率逐年增加,目前成为我国成年人中最常见的慢性肝病之一。NAFLD可由非酒精性肝脂肪变性进展为非酒精性脂肪性肝炎、肝硬化、肝细胞癌及NAFLD相关性心血管事件、死亡等重大疾病。现对NAFLD发生的危险因素以及进展为肝纤维化、肝硬化、肝癌、相关心血管事件和死亡等重大疾病的相关危险因素进行综述,以便进一步探讨NAFLD发生发展的机制,降低NAFLD的患病率,减缓NAFLD的进展程度,降低相关疾病的病死率。     

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.

     

肠道菌群与非酒精性脂肪性肝病研究进展

非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)发病率不断升高,对其发生、发展及防治研究变得极为迫切。近年来肠道菌群被认为是机体一个重要的"特殊器官",参与机体代谢及相关疾病的发生、发展,与NAFLD关系密切。本文就肠道菌群与NAFLD的关系研究进行综述。     

omega-3多不饱和脂肪酸治疗非酒精性脂肪性肝病的研究进展

随着人们生活方式和饮食结构的改变,非酒精性脂肪性肝病(NAFLD)发病率逐年上升,严重威胁人类健康。NAFLD疗法一直是基础和临床肝病研究的热门领域。近年来,诸多研究揭示omega-3多不饱和脂肪酸(ω3-PUFA)可促进脂肪酸氧化并改善肠道稳态,从而改善脂代谢和肝脏炎症,因而越来越多的临床研究开始将ω3-PUFA运用于NAFLD的治疗中。然而,ω3-PUFA治疗NAFLD的机制尚不明确,相关临床研究也存在一定局限性。主要介绍了ω3-PUFA在NAFLD中发挥的作用以及相关的临床研究结果,并进一步讨论ω3-PUFA治疗NAFLD尚需解决的问题。     

Characteristics of intestinal bacteria with fatty liver diseases and cirrhosis

Non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) are significant health burdens worldwide with a substantial rise in prevalence. Both can progress to liver cirrhosis. Recent studies have shown that the gut microbiome was associated with NAFLD/AFLD development and progression. The present review focuses on the characteristics of bacteria in NAFLD, AFLD and liver cirrhosis. The similarities and differences of intestinal bacteria are discussed.This study reviews the existing literatures on the microbiota, fatty liver disease, and liver cirrhosis based on Pubmed database.The study showed NAFLD was characterized by increased amounts of Lachnospiraceae from the phylum Firmicutes and Roseburia from the Lachnospiraceae family, and the proportion of Enterobacteria and Proteobacteria was increased after alcohol intake. Reduced Bacteroidetes was observed in cirrhosis. Microbiota can improve or aggravate the above liver diseases through several mechanisms, like increasing liver lipid metabolism, increasing alcohol production, increasing intestinal permeability, bacterial translocation, intestinal bacterial overgrowth, enteric dysbiosis, and impairing bile secretion.Different hepatic diseases owned different intestinal bacterial characters. Microbiota can improve or aggravate three kinds of liver diseases through several mechanisms. However, the depletion of these bacteria is needed to verify their role in liver disease.     

Liver fat as risk factor of hepatic and cardiometabolic diseases

Non-alcoholic fatty liver disease (NAFLD) is a disorder characterized by excessive accumulation of fat in the liver that can progress to liver inflammation (non-alcoholic steatohepatitis [NASH]), liver fibrosis, and cirrhosis. Although most efforts for drug development are focusing on the treatment of the latest stages of NAFLD, where significant fibrosis and NASH are present, findings from studies suggest that the amount of liver fat may be an important independent risk factor and/or predictor of development and progression of NAFLD and metabolic diseases. In this review, we first describe the current tools available for quantification of liver fat in humans and then present the clinical and pathophysiological evidence that link liver fat with NAFLD progression as well as with cardiometabolic diseases. Finally, we discuss current pharmacological and non-pharmacological approaches to reduce liver fat and present open questions that have to be addressed in future studies.