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

惠登城; 孙明瑜

doi:10.3969/j.issn.1001-5256.2020.07.039

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

DOI: 10.3969/j.issn.1001-5256.2020.07.039

上海中医药大学附属曙光医院，上海中医药大学肝病研究所肝肾疾病病证教育部重点实验室

基金项目:

国家中医药管理局第四批中医优才(2017-124);国家中医药管理局中医肝胆病重点学科、慢性肝病虚损重点研究室和上海市中医临床重点实验室资助项目；上海市科委专项(19401972300)；上海中医药大学研究生创新课程建设(2017)；

详细信息

中图分类号: R575.5
计量
- 文章访问数: 889
- HTML全文浏览量: 30
- PDF下载量: 172
- 被引次数: 0
出版历程
- 出版日期: 2020-07-20

Association between nonalcoholic fatty liver disease and gut microbiota based on the theory of gut-liver axis

Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

Research funding:

摘要

摘要:
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。
- 非酒精性脂肪性肝病 /
- 胃肠道微生物组 /
- 肠-肝轴
Abstract:
Nonalcoholic fatty liver disease( NAFLD) has become the most important chronic liver disease and is recognized as the hepatic manifestation of metabolic syndrome,which may progress to liver fibrosis,liver cirrhosis,and even hepatocellular carcinoma in the advanced stage. Gut microbiota,as important symbiotic organisms in the human body,affects metabolic function and may be closely associated with NAFLD,and the theory of gut-liver axis provides a theoretical basis for understanding that intestinal dysbacteriosis may cause liver pathological changes. This article explores the association between NAFLD and gut microbiota,so as to lay a theoretical foundation for the future research on the therapy for NAFLD targeting gut microbiota.
- non-alcoholic fatty liver disease /
- gastrointestinal microbiome /
- gut-liver axis

HTML全文

参考文献(47)

[1]TOMIC D,KEMP WW,ROBERTS SK.Nonalcoholic fatty liver disease:Current concepts,epidemiology and management strategies[J].Eur J Gastroenterol Hepatol,2018,30(10):1103-1115．

[2]PERUMPAIL BJ,KHAN MA,YOO ER,et al.Clinical epidemiology and disease burden of nonalcoholic fatty liver disease[J].World JGastroenterol,2017,23(47):8263-8276．

[3]POWER SE,O'TOOLE PW,STANTON C,et al.Intestinal microbiota,diet and health[J].Br J Nutr,2014,111(3):387-402．

[4]TRIPATHI A,DEBELIUS J,BRENNER DA,et al.The gut-liver axis and the intersection with the microbiome[J].Nat Rev Gastroenterol Hepatol,2018,15(7):397-411．

[5]KOLODZIEJCZYK AA,ZHENG D,SHIBOLET O,et al.The role of the microbiome in NAFLD and NASH[J].EMBO Mol Med,2019,11(2):e9302．

[6]DE LA SERRE CB,ELLIS CL,LEE J,et al.Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation[J].Am J Physiol Gastrointest Liver Physiol,2010,299(2):G440-G448．

[7]ZHU L,BAKER SS,GILL C,et al.Characterization of gut microbiomes in nonalcoholic steatohepatitis(NASH)patients:A connection between endogenous alcohol and NASH[J].Hepatology,2013,57(2):601-609．

[8]MICHAIL S,LIN M,FREY MR,et al.Altered gut microbial energy and metabolism in children with non-alcoholic fatty liver disease[J].FEMS Microbiol Ecol,2015,91(2):1-9．

[9]YUAN J,CHEN C,CUI JH,et al.Fatty liver disease caused by high-alcohol-producing klebsiella pneumoniae[J].Cell metabolism,2019,30(4):675-688.e7．

[10]VANCAMELBEKE M,VERMEIRE S.The intestinal barrier:A fundamental role in health and disease[J].Expert Rev Gastroenterol Hepatol,2017,11(9):821-834．

[11]MIURA K,OHNISHI H.Role of gut microbiota and Toll-like receptors in nonalcoholic fatty liver disease[J].World J Gastroenterol,2014,20(23):7381-7391．

[12]KRAWCZYK M,MACIEJEWSKA D,RYTERSKA K,et al.Gut permeability might be improved by dietary fiber in individuals with nonalcoholic fatty liver disease(NAFLD)undergoing weight reduction[J].Nutrients,2018,10(11):1793．

[13]HENDY OM,ELSABAAWY MM,AREF MM,et al.Evaluation of circulating zonulin as a potential marker in the pathogenesis of nonalcoholic fatty liver disease[J].APMIS,2017,125(7):607-613．

[14]RUIZ AG,CASAFONT F,CRESPO J,et al.Lipopolysaccharidebinding protein plasma levels and liver TNF-alpha gene expression in obese patients:Evidence for the potential role of endotoxin in the pathogenesis of non-alcoholic steatohepatitis[J].Obes Surg,2007,17(10):1374-1380．

[15]CAESAR R,REIGSTAD CS,BCKHED HK,et al.Gut-derived lipopolysaccharide augments adipose macrophage accumulation but is not essential for impaired glucose or insulin tolerance in mice[J].Gut,2012,61(12):1701-1707．

[16]DAPITO DH,MENCIN A,GWAK GY,et al.Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4[J].Cancer Cell,2012,21(4):504-516．

[17]SHERRIFF JL,O'SULLIVAN TA,PROPERZI C,et al.Choline,Its potential role in nonalcoholic fatty liver disease,and the case for human and bacterial genes[J].Adv Nutr,2016,7(1):5-13．

[18]WALKER AK,JACOBS RL,WATTS JL,et al.A conserved SREBP-1/phosphatidylcholine feedback circuit regulates lipogenesis in metazoans[J].Cell,2011,147(4):840-852．

[19]AUGUSTYN M,GRYS I,KUKLA M.Small intestinal bacterial overgrowth and nonalcoholic fatty liver disease[J].Clin Exp Hepatol,2019,5(1):1-10．

[20]WANG Z,KLIPFELL E,BENNETT BJ,et al.Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease[J].Nature,2011,472(7341):57-63．

[21]TARANTINO G,CAPUTI A.JNKs,insulin resistance and inflammation:A possible link between NAFLD and coronary artery disease[J].World JGastroenterol,2011,17(33):3785-3794．

[22] SAAD MJ,SANTOS A,PRADA PO.Linking gut microbiota and inflammation to obesity and insulin resistance[J].Physiology(Bethesda),2016,31(4):283-293．

[23]GONZALEZ-GAY MA,DE MATIAS JM,GONZALEZ-JUANATEY C,et al.Anti-tumor necrosis factor-alpha blockade improves insulin resistance in patients with rheumatoid arthritis[J].Clin Exp Rheumatol,2006,24(1):83-86．

[24]MA X,HUA J,LI Z.Probiotics improve high fat diet-induced hepatic steatosis and insulin resistance by increasing hepatic NKT cells[J].J Hepatol,2008,49(5):821-830．

[25]FANG YL,CHEN H,WANG CL,et al.Pathogenesis of non-alcoholic fatty liver disease in children and adolescence:From“two hit theory”to“multiple hit model”[J].World J Gastroenterol,2018,24(27):2974-2983．

[26]MA J,ZHOU Q,LI H.Gut microbiota and nonalcoholic fatty liver disease:Insights on mechanisms and therapy[J].Nutrients,2017,9(10):1124．

[27]PAREDES-TURRUBIARTE G,GONZLEZ-CHVEZ A,PREZ-TAMAYO R,et al.Severity of non-alcoholic fatty liver disease is associated with high systemic levels of tumor necrosis factor alpha and low serum interleukin 10 in morbidly obese patients[J].Clin Exp Med,2016,16(2):193-202．

[28]STIENSTRA R,SAUDALE F,DUVAL C,et al.Kupffer cells promote hepatic steatosis via interleukin-1beta-dependent suppression of peroxisome proliferator-activated receptor alpha activity[J].Hepatology,2010,51(2):511-522．

[29]CHU H,DUAN Y,YANG L,et al.Small metabolites,possible big changes:A microbiota-centered view of non-alcoholic fatty liver disease[J].Gut,2019,68(2):359-370．

[30]FUCHS C,CLAUDEL T,TRAUNER M.Bile acid-mediated control of liver triglycerides[J].Semin Liver Dis,2013,33(4):330-342．

[31]JIAO N,BAKER SS,CHAPA-RODRIGUEZ A,et al.Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD[J].Gut,2018,67(10):1881-1891．

[32]LOOMBA R,SEGURITAN V,LI W,et al.Gut microbiome-based metagenomic signature for non-invasive detection of advanced fibrosis in human nonalcoholic fatty liver disease[J].Cell Metab,2019,30(3):607．

[33]CANI PD,AMAR J,IGLESIAS MA,et al.Metabolic endotoxemia initiates obesity and insulin resistance[J].Diabetes,2007,56(7):1761-1772．

[34]GANGARAPU V,INCE AT,BAYSAL B,et al.Efficacy of rifaximin on circulating endotoxins and cytokines in patients with nonalcoholic fatty liver disease[J].Eur J Gastroenterol Hepatol,2015,27(7):840-845．

[35]HWANG I,PARK YJ,KIM YR,et al.Alteration of gut microbiota by vancomycin and bacitracin improves insulin resistance via glucagon-like peptide 1 in diet-induced obesity[J].FASEB J,2015,29(6):2397-2411．

[36]CHEN J,WANG R,LI XF,et al.Bifidobacterium adolescentis supplementation ameliorates visceral fat accumulation and insulin sensitivity in an experimental model of the metabolic syndrome[J].Br J Nutr,2012,107(10):1429-1434．

[37]NABAVI S,RAFRAF M,SOMI MH,et al.Effects of probiotic yogurt consumption on metabolic factors in individuals with nonalcoholic fatty liver disease[J].J Dairy Sci,2014,97(12):7386-7393．

[38]LOMAN BR,HERNNDEZ-SAAVEDRA D,AN R,et al.Prebiotic and probiotic treatment of nonalcoholic fatty liver disease:A systematic review and meta-analysis[J].Nutr Rev,2018,76(11):822-839．

[39]XU JH,LIU XZ,PAN W,et al.Berberine protects against diet-induced obesity through regulating metabolic endotoxemia and gut hormone levels[J].Mol Med Rep,2017,15(5):2765-2787．

[40]LI C,HE JZ,ZHOU XD,et al.Berberine regulates type 2 diabetes mellitus related with insulin resistance[J].China J Chin Mater Med,2017,42(12):2254-2260.(in Chinese)李骋，何金枝，周学东，等．黄连素调控胰岛素抵抗相关2型糖尿病的研究进展[J]．中国中药杂志，2017,42(12):2254-2260．

[41]ZHANG X,ZHAO Y,ZHANG M,et al.Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats[J].PLo S One,2012,7(8):e42529．

[42]CHARYTONIUK T,DRYGALSKI K,KONSTANTYNOWICZ-NOWICKAK,et al.Alternative treatment methods attenuate the development of NAFLD:A review of resveratrol molecular mechanisms and clinical trials[J].Nutrition,2017,34:108-117．

[43]LI R,LI J,HUANG Y,et al.Polydatin attenuates diet-induced nonalcoholic steatohepatitis and fibrosis in mice[J].Int J Biol Sci,2018,14(11):1411-1425．

[44]CHAPLIN A,CARPNC,MERCADER J.Resveratrol,metabolic syndrome,and gut microbiota[J].Nutrients,2018,10(11):1651．

[45]ZHANG Y,TANG K,DENG Y,et al.Effects of shenling baizhu powder herbal formula on intestinal microbiota in high-fat diet-induced NAFLD rats[J].Biomed Pharmacother,2018,102:1025-1036．

[46]ESLAM M,SANYAL AJ,GEORGE J,et al.MAFLD:A consensus-driven proposed nomenclature for metabolic associated fatty liver disease[J].Gastroenterology,2020,158(7):1999-2014.e1．

[47]ZHANG DY,ZHU L,LIU HN,et al.The protective effect and mechanism of the FXR agonist obeticholic acid via targeting gut microbiota in non-alcoholic fatty liver disease[J].Drug Des Devel Ther,2019,13:2249-2270.

施引文献

资源附件(0)

访问统计