肠道微生态失调对非酒精性脂肪肝影响的研究进展
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摘要
<正>非酒精性脂肪肝(nonalcoholic fatty liver disease,NAFLD)是指不存在过量饮酒或其他已知肝脏疾病,肝脏中脂肪堆积~([1]),其主要病理特征是肝细胞脂肪变性(超过5%～10%的肝细胞具有肉眼可见的脂肪变性)~([2])。NAFLD的发展过程包括从简单的肝脏脂肪堆积到非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)肝硬化和肝细胞癌(hepatocellular carcinoma,HCC)~([3])。近年来,NAFLD患
引文
[1]Than N N,Newsome P N.A concise review of non-alcoholic fatty liver disease[J].Atherosclerosis,2015,239(1):192-202
[2]Neuschwander-Tetri B A,Caldwell S H.Nonalcoholic steatohepatitis:summary of an AASLD single topic conference[J].Hepatology,2003,37(5):1202-1219.
[3]Willebrords J,Pereira I V A,Maes M,et al.Strategies,models and biomarkers in experimental non-alcoholic fatty liver disease research[J].Progress in Lipid Research,2015,59:106-125.
[4]Younossi Z M,Koenig A B,Abdelatif D,et al.Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence,incidence,and outcomes[J].Hepatology,2016,64(1):73-84.
[5]Yaru Li,Jing Wang,Yuhan Tang,et al.Bidirectional association between nonalcoholic fatty liver disease and type 2diabetes in Chinese population:Evidence from the DongfengTongji cohort study[J].PLoS One,2017,12(3):0174291
[6]Mikolasevic I,Milic S,Turk Wensveen T,et al.Nonalcoholic fatty liver disease-A multisystem disease[J].World JGastroenterol.2016,;22(43):9488-9505.
[7]Willebrords J,Pereira IVA,Maes M,et al.Strategies,models and biomarkers in experimental non-alcoholic fatty liver disease research[J].Prog Lipid Res,2015,59:106-125.
[8]Buzzetti E,Pinzani M,Tsochatzis E A.The multiple-hit pathogenesis of non-alcoholic fatty liver disease(NAFLD)[J].Metabolism,2016,65(8):1038-1048.
[9]Spencer M D,Hamp T J,Reid R W,et al.Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency[J].Gastroenterology,2011,140(3):976-986.
[10]Miyake Y,Yamamoto k.Role of gut microbiota in liver disesses[J].Hepatol Res,2013,43(2):139-146
[11]Ron Sender,Shai Fuchs,Ron Milo.Revised Estimates for the Number of Human and Bacteria Cells in the Body[J].Plos Biol,2016,14(8):1002533.
[12]Vajro P,Lenta S,Socha P,et al.Diagnosis of nonalcoholic fatty liver disease in children and adolescents:position paper of the ESPGHAN Hepatology Committee[J].Pediatr Gastreenterol Nutr,2012,54(5):700-713.
[13]Athyros V G,Tziomalos K,Katsiki N,et al.Cardiovascular risk across the histological spectrum and the clinical manifestations of non-alcoholic fatty liver disease:An update[J].World J Gastroenterol,2015,21(22):6820-6834.
[14]Larsen N,Vogensen F K,van den Berg F W J,et al.Gut microbiota in human adults with type 2diabetes differs from non-diabetic adults[J].PLoS One,2010,5(2):9085.
[15]Wang Z,Klipfell E,Bennett B J,et al.Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease[J].Nature,2011,472(7341):57-63.
[16]Murphy E F,Cotter P D,Hogan A,et al.Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity[J].Gut,2013,62(2):220-226.
[17]Turnbaugh P J,Hamady M,Yatsunenko T,et al.A core gut microbiome in obese and lean twins[J].Nature,2009,457(7228):480-484.
[18]Erika Utzeri.Paolo Usai,Role of non-steroidal antiinflammatory drugs on intestinal permeability and nonalcoholic fatty liver disease[J].World J Gastroenterol,2017,23(22):3954-3963.
[19]Zorn A M,Wells J M.Vertebrate endoderm development and organ formation[J].Annu.Rev.Cell Dev Biol,2009,25:221-251.
[20]Jia W,Rajani C.The Influence of Gut Microbial Metabolism on the Development and Progression of Non-alcoholic Fatty Liver Disease[J].Adv Exp Med Biol,2018,1061:95-110.
[21]Rahman K,Desai C,Iyer S S,et al.Loss of junctional adhesion molecule a promotes severe steatohepatitis in mice on a diet high in saturated fat,fructose,and cholesterol[J].Gastroenterology,2016,151(4):733-746.
[22]Miele L C,Valenza V,La Torre G,et al.Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease[J].Hepatology,2009,49(6):1877-1887.
[23]Luther J,Garber J J,Khalili H,et al.Hepatic injury in nonalcoholic steatohepatitis contributes to altered intestinal permeability[J].Cell Mol Gastroenterol Hepatol,2015,1(2):222-232.
[24]Schnabl B,Brenner D A.Interactions between the intestinal microbiome and liver diseases[J].Gastroenterology,2014,146(6):1513-1524.
[25]Mouzaki M,Comelli E M,Arendt B M,et al.Intestinal microbiota in patients with nonalcoholic fatty liver disease[J].Hepatology,2013,58(1):120-127.
[26]Hotamisligil G S.Inflammation and metabolic disorders[J].Nature,2006,444(7121):860-867.
[27]Wullaert A,van Loo G,Heyninck K,et al.Hepatic tumor necrosis factor signaling and nuclear factor-κb:effects on liver homeostasis and beyond[J].Endocr Rev,2007,28(4):365-386.
[28]Wesolowski S R,Kasmi K C Jonscher K R,et al.Developmental origins of NAFLD:a womb with a clue[J].Nat Rev Gastroenterol Hepatol,2017,14(2):81-96.
[29]Kawai T,Akira S.The role of pattern-recognition receptors in innate immunity:update on Toll-like receptors[J].Nat Immunol,2010,11(5):373-384.
[30]Miura K,Kodama Y,Inokochi S,et al.Toll-like receptor promotes steatohepatitis by induction of interleukin-1βin mice[J]Gastroenterology,2010,139(1)323-334.
[31]Miura K,Ohnishi H.Role of gut microbiota and Toll-like receptors in nonalcoholic fatty liver disease[J].World JGastroenterol,2014,20(23):7381-7391.
[32]Cope K,Risby T,Diehl A M.Increased gastrointestinal ethanol production in obese mice:implications for fatty liver disease pathogenesis[J].Gastroenterology,2000,119(5):1340-1347.
[33]Zhu L,Baker S S,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.
[34]Engstler A J,Aumiller T,Degen C,et al.Insulin resistance alters hepatic ethanol metabolism:studies in mice and children with non-alcoholic fatty liver disease[J].Gut,2016,65(9):1564-1571.
[35]Dumas M E,Kinross J,Nicholson J K.Metabolic phenotyping and systems biology approaches to understanding metabolic syndrome and fatty liver disease[J].Gastroenterology,2014,146(1):46-62.
[36]Jiang C,Xie C,Li F,et al.Intestinal farnesoid x receptor signaling promotes nonalcoholic fatty liver disease[J].J Clin Invest,2015,125(1):386-402.
[37]Wahlstr m A,Kovatcheva-Datchary P,St hlman M,et al.Crosstalk between bile acids and gut microbiota and its impact on farnesoid x receptor signalling[J].Dig Dis,2017,35(3):246-250.
[38]Renga B,Mencarelli A,Cipriani S,et al.The bile acid sensor FXR is required for immune-regulatory activities of TLR-9in intestinal inflammation[J].PLoS One,2013,8(1):54472.
[39]叶春,房宇.非酒精性脂肪肝大鼠血清氨基酸谱的改变及分析[J].南京师大学报(自然科学版),2016,39(1):90-94.
[40]江向洋.肠道菌群与NAFLD发生发展的关联代谢机制研究[D].杭州:浙江大学,2017:6-8.
[41]Karczewski J,Troost F J,Konings L,et al.Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier[J].Am J Physiol Gastrointest Liver Physiol,2010,298(6):851-859.
[42]Ritze Y,Bárdos G,Claus A,et al.Lactobacillus rhamnosus GG protects against non-alcoholic fatty liver disease in mice[J].PLoS One,2014,9(1):80169.
[43]Hu J J,Luo H H,Jiang Y,et al.Dietary capsaicin and antibiotics act synergistically to reduce non-alcoholic fatty liver disease induced by high fat diet in mice[J].Oncotarget,2017,8(24):38161-38175.
[44]Xie G,Wang X,Huang F,et al.Dysregulated hepatic bile acids collaboratively promote liver carcinogenesis[J].Int JCancer,2016,139(8):1764-1775.
[45]Su D,Nie Y,Zhu A,et al.Vitamin D signaling through induction of paneth cell defensins maintains gut microbiota and improves metabolic disorders and hepatic steatosis in animal models[J].Front Physiol,2016,7:498.
[2]Neuschwander-Tetri B A,Caldwell S H.Nonalcoholic steatohepatitis:summary of an AASLD single topic conference[J].Hepatology,2003,37(5):1202-1219.
[3]Willebrords J,Pereira I V A,Maes M,et al.Strategies,models and biomarkers in experimental non-alcoholic fatty liver disease research[J].Progress in Lipid Research,2015,59:106-125.
[4]Younossi Z M,Koenig A B,Abdelatif D,et al.Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence,incidence,and outcomes[J].Hepatology,2016,64(1):73-84.
[5]Yaru Li,Jing Wang,Yuhan Tang,et al.Bidirectional association between nonalcoholic fatty liver disease and type 2diabetes in Chinese population:Evidence from the DongfengTongji cohort study[J].PLoS One,2017,12(3):0174291
[6]Mikolasevic I,Milic S,Turk Wensveen T,et al.Nonalcoholic fatty liver disease-A multisystem disease[J].World JGastroenterol.2016,;22(43):9488-9505.
[7]Willebrords J,Pereira IVA,Maes M,et al.Strategies,models and biomarkers in experimental non-alcoholic fatty liver disease research[J].Prog Lipid Res,2015,59:106-125.
[8]Buzzetti E,Pinzani M,Tsochatzis E A.The multiple-hit pathogenesis of non-alcoholic fatty liver disease(NAFLD)[J].Metabolism,2016,65(8):1038-1048.
[9]Spencer M D,Hamp T J,Reid R W,et al.Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency[J].Gastroenterology,2011,140(3):976-986.
[10]Miyake Y,Yamamoto k.Role of gut microbiota in liver disesses[J].Hepatol Res,2013,43(2):139-146
[11]Ron Sender,Shai Fuchs,Ron Milo.Revised Estimates for the Number of Human and Bacteria Cells in the Body[J].Plos Biol,2016,14(8):1002533.
[12]Vajro P,Lenta S,Socha P,et al.Diagnosis of nonalcoholic fatty liver disease in children and adolescents:position paper of the ESPGHAN Hepatology Committee[J].Pediatr Gastreenterol Nutr,2012,54(5):700-713.
[13]Athyros V G,Tziomalos K,Katsiki N,et al.Cardiovascular risk across the histological spectrum and the clinical manifestations of non-alcoholic fatty liver disease:An update[J].World J Gastroenterol,2015,21(22):6820-6834.
[14]Larsen N,Vogensen F K,van den Berg F W J,et al.Gut microbiota in human adults with type 2diabetes differs from non-diabetic adults[J].PLoS One,2010,5(2):9085.
[15]Wang Z,Klipfell E,Bennett B J,et al.Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease[J].Nature,2011,472(7341):57-63.
[16]Murphy E F,Cotter P D,Hogan A,et al.Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity[J].Gut,2013,62(2):220-226.
[17]Turnbaugh P J,Hamady M,Yatsunenko T,et al.A core gut microbiome in obese and lean twins[J].Nature,2009,457(7228):480-484.
[18]Erika Utzeri.Paolo Usai,Role of non-steroidal antiinflammatory drugs on intestinal permeability and nonalcoholic fatty liver disease[J].World J Gastroenterol,2017,23(22):3954-3963.
[19]Zorn A M,Wells J M.Vertebrate endoderm development and organ formation[J].Annu.Rev.Cell Dev Biol,2009,25:221-251.
[20]Jia W,Rajani C.The Influence of Gut Microbial Metabolism on the Development and Progression of Non-alcoholic Fatty Liver Disease[J].Adv Exp Med Biol,2018,1061:95-110.
[21]Rahman K,Desai C,Iyer S S,et al.Loss of junctional adhesion molecule a promotes severe steatohepatitis in mice on a diet high in saturated fat,fructose,and cholesterol[J].Gastroenterology,2016,151(4):733-746.
[22]Miele L C,Valenza V,La Torre G,et al.Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease[J].Hepatology,2009,49(6):1877-1887.
[23]Luther J,Garber J J,Khalili H,et al.Hepatic injury in nonalcoholic steatohepatitis contributes to altered intestinal permeability[J].Cell Mol Gastroenterol Hepatol,2015,1(2):222-232.
[24]Schnabl B,Brenner D A.Interactions between the intestinal microbiome and liver diseases[J].Gastroenterology,2014,146(6):1513-1524.
[25]Mouzaki M,Comelli E M,Arendt B M,et al.Intestinal microbiota in patients with nonalcoholic fatty liver disease[J].Hepatology,2013,58(1):120-127.
[26]Hotamisligil G S.Inflammation and metabolic disorders[J].Nature,2006,444(7121):860-867.
[27]Wullaert A,van Loo G,Heyninck K,et al.Hepatic tumor necrosis factor signaling and nuclear factor-κb:effects on liver homeostasis and beyond[J].Endocr Rev,2007,28(4):365-386.
[28]Wesolowski S R,Kasmi K C Jonscher K R,et al.Developmental origins of NAFLD:a womb with a clue[J].Nat Rev Gastroenterol Hepatol,2017,14(2):81-96.
[29]Kawai T,Akira S.The role of pattern-recognition receptors in innate immunity:update on Toll-like receptors[J].Nat Immunol,2010,11(5):373-384.
[30]Miura K,Kodama Y,Inokochi S,et al.Toll-like receptor promotes steatohepatitis by induction of interleukin-1βin mice[J]Gastroenterology,2010,139(1)323-334.
[31]Miura K,Ohnishi H.Role of gut microbiota and Toll-like receptors in nonalcoholic fatty liver disease[J].World JGastroenterol,2014,20(23):7381-7391.
[32]Cope K,Risby T,Diehl A M.Increased gastrointestinal ethanol production in obese mice:implications for fatty liver disease pathogenesis[J].Gastroenterology,2000,119(5):1340-1347.
[33]Zhu L,Baker S S,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.
[34]Engstler A J,Aumiller T,Degen C,et al.Insulin resistance alters hepatic ethanol metabolism:studies in mice and children with non-alcoholic fatty liver disease[J].Gut,2016,65(9):1564-1571.
[35]Dumas M E,Kinross J,Nicholson J K.Metabolic phenotyping and systems biology approaches to understanding metabolic syndrome and fatty liver disease[J].Gastroenterology,2014,146(1):46-62.
[36]Jiang C,Xie C,Li F,et al.Intestinal farnesoid x receptor signaling promotes nonalcoholic fatty liver disease[J].J Clin Invest,2015,125(1):386-402.
[37]Wahlstr m A,Kovatcheva-Datchary P,St hlman M,et al.Crosstalk between bile acids and gut microbiota and its impact on farnesoid x receptor signalling[J].Dig Dis,2017,35(3):246-250.
[38]Renga B,Mencarelli A,Cipriani S,et al.The bile acid sensor FXR is required for immune-regulatory activities of TLR-9in intestinal inflammation[J].PLoS One,2013,8(1):54472.
[39]叶春,房宇.非酒精性脂肪肝大鼠血清氨基酸谱的改变及分析[J].南京师大学报(自然科学版),2016,39(1):90-94.
[40]江向洋.肠道菌群与NAFLD发生发展的关联代谢机制研究[D].杭州:浙江大学,2017:6-8.
[41]Karczewski J,Troost F J,Konings L,et al.Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier[J].Am J Physiol Gastrointest Liver Physiol,2010,298(6):851-859.
[42]Ritze Y,Bárdos G,Claus A,et al.Lactobacillus rhamnosus GG protects against non-alcoholic fatty liver disease in mice[J].PLoS One,2014,9(1):80169.
[43]Hu J J,Luo H H,Jiang Y,et al.Dietary capsaicin and antibiotics act synergistically to reduce non-alcoholic fatty liver disease induced by high fat diet in mice[J].Oncotarget,2017,8(24):38161-38175.
[44]Xie G,Wang X,Huang F,et al.Dysregulated hepatic bile acids collaboratively promote liver carcinogenesis[J].Int JCancer,2016,139(8):1764-1775.
[45]Su D,Nie Y,Zhu A,et al.Vitamin D signaling through induction of paneth cell defensins maintains gut microbiota and improves metabolic disorders and hepatic steatosis in animal models[J].Front Physiol,2016,7:498.