期刊文献+

Role of gut microbiota and Toll-like receptors in nonalcoholic fatty liver disease 被引量:80

Role of gut microbiota and Toll-like receptors in nonalcoholic fatty liver disease
下载PDF
导出
摘要 Emerging data have shown a close association between compositional changes in gut microbiota and the development of nonalcoholic fatty liver disease(NAFLD).The change in gut microbiota may alter nutritional absorption and storage.In addition,gut microbiota are a source of Toll-like receptor(TLR)ligands,and their compositional change can also increase the amount of TLR ligands delivered to the liver.TLR ligands can stimulate liver cells to produce proinflammatory cytokines.Therefore,the gut-liver axis has attracted much interest,particularly regarding the pathogenesis of NAFLD.The abundance of the major gut microbiota,including Firmicutes and Bacteroidetes,has been considered a potential underlying mechanism of obesity and NAFLD,but the role of these microbiota in NAFLD remains unknown.Several reports have demonstrated that certain gut microbiota are associated with the development of obesity and NAFLD.For instance,a decrease in Akkermansia muciniphila causes a thinner intestinal mucus layer and promotes gut permeability,which allows the leakage of bacterial components.Interventions to increase Akkermansia muciniphila improve the metabolic parameters in obesity and NAFLD.In children,the levels of Escherichia were significantly increased in nonalcoholic steatohepatitis(NASH)compared with those in obese control.Escherichia can produce ethanol,which promotes gut permeability.Thus,normalization of gut microbiota using probiotics or prebiotics is a promising treatment option for NAFLD.In addition,TLR signaling in the liver is activated,and its downstream molecules,such as proinflammatory cytokines,are increased in NAFLD.To data,TLR2,TLR4,TLR5,and TLR9 have been shown to be associated with the pathogenesis of NAFLD.Therefore,gut microbiota and TLRs are targets for NAFLD treatment. Emerging data have shown a close association between compositional changes in gut microbiota and the development of nonalcoholic fatty liver disease (NAFLD). The change in gut microbiota may alter nutritional absorption and storage. In addition, gut microbiota are a source of Toll-like receptor (TLR) ligands, and their compositional change can also increase the amount of TLR ligands delivered to the liver. TLR ligands can stimulate liver cells to produce proinflammatory cytokines. Therefore, the gut-liver axis has attracted much interest, particularly regarding the pathogenesis of NAFLD. The abundance of the major gut microbiota, including Firmicutes and Bacteroidetes, has been considered a potential underlying mechanism of obesity and NAFLD, but the role of these microbiota in NAFLD remains unknown. Several reports have demonstrated that certain gut microbiota are associated with the development of obesity and NAFLD. For instance, a decrease in Akkermansia muciniphila causes a thinner intestinal mucus layer and promotes gut permeability, which allows the leakage of bacterial components. Interventions to increase Akkermansia muciniphila improve the metabolic parameters in obesity and NAFLD. In children, the levels of Escherichia were significantly increased in nonalcoholic steatohepatitis (NASH) compared with those in obese control. Escherichia can produce ethanol, which promotes gut permeability. Thus, normalization of gut microbiota using probiotics or prebiotics is a promising treatment option for NAFLD. In addition, TLR signaling in the liver is activated, and its downstream molecules, such as proinflammatory cytokines, are increased in NAFLD. To data, TLR2, TLR4, TLR5, and TLR9 have been shown to be associated with the pathogenesis of NAFLD. Therefore, gut microbiota and TLRs are targets for NAFLD treatment.
出处 《World Journal of Gastroenterology》 SCIE CAS 2014年第23期7381-7391,共11页 世界胃肠病学杂志(英文版)
基金 Supported by JSPS[Grant-in-Aid for Scientific Research(C)](to Miura K)
关键词 Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Gut microbiota Toll-like receptor PROBIOTICS PREBIOTICS Nonalcoholic fatty liver disease Nonalcoholic stea
  • 相关文献

参考文献11

  • 1Ya-Ping Zhang Xi-Xian Yao Xia Zhao.Interleukin-1 beta up-regulates tissue inhibitor of matrix metalloproteinase-1 mRNA and phosphorylation of c-jun N-terminal kinase and p38 in hepatic stellate cells[J].World Journal of Gastroenterology,2006,12(9):1392-1396. 被引量:22
  • 2Kento Imajo,Koji Fujita,Masato Yoneda,Yuichi Nozaki,Yuji Ogawa,Yoshiyasu Shinohara,Shingo Kato,Hironori Mawatari,Wataru Shibata,Hiroshi Kitani,Kenichi Ikejima,Hiroyuki Kirikoshi,Noriko Nakajima,Satoru Saito,Shiro Maeyama,Sumio Watanabe,Koichiro Wada,Atsushi Nakajima.Hyperresponsivity to Low-Dose Endotoxin during Progression to Nonalcoholic Steatohepatitis Is Regulated by Leptin-Mediated Signaling[J].Cell Metabolism.2012(1)
  • 3Swaroop Pendyala,Jeanne M. Walker,Peter R. Holt.A High-Fat Diet Is Associated With Endotoxemia That Originates From the Gut[J].Gastroenterology.2012(5)
  • 4Yehuda Kamari,Aviv Shaish,Einav Vax,Shay Shemesh,Michal Kandel-Kfir,Yaron Arbel,Sarita Olteanu,Iris Barshack,Shahar Dotan,Elana Voronov,Charles A. Dinarello,Ron N. Apte,Dror Harats.Lack of interleukin-1α or interleukin-1β inhibits transformation of steatosis to steatohepatitis and liver fibrosis in hypercholesterolemic mice[J].Journal of Hepatology.2011(5)
  • 5Erwin G?bele,Karin Dostert,Claudia Hofmann,Reiner Wiest,Jürgen Sch?lmerich,Claus Hellerbrand,Florian Obermeier.DSS induced colitis increases portal LPS levels and enhances hepatic inflammation and fibrogenesis in experimental NASH[J].Journal of Hepatology.2011(6)
  • 6J. A. Ehses,D. T. Meier,S. Wueest,J. Rytka,S. Boller,P. Y. Wielinga,A. Schraenen,K. Lemaire,S. Debray,L. Lommel,J. A. Pospisilik,O. Tschopp,S. M. Schultze,U. Malipiero,H. Esterbauer,H. Ellingsgaard,S. Rütti,F. C. Schuit,T. A. Lutz,M. B?ni-Schnetzler,D. Konrad,Marc Y. Donath.Toll-like receptor 2-deficient mice are protected from insulin resistance and beta cell dysfunction induced by a high-fat diet[J].Diabetologia.2010(8)
  • 7Kouichi Miura,Yuzo Kodama,Sayaka Inokuchi,Bernd Schnabl,Tomonori Aoyama,Hirohide Ohnishi,Jerrold M. Olefsky,David A. Brenner,Ekihiro Seki.Toll-Like Receptor 9 Promotes Steatohepatitis by Induction of Interleukin-1β in Mice[J].Gastroenterology.2010(1)
  • 8Navdeep Dhillon,Liron Walsh,Bernd Krüger,Stephen C. Ward,James H. Godbold,Mohamed Radwan,Thomas Schiano,Barbara T. Murphy,Bernd Schr?ppel.A single nucleotide polymorphism of Toll-like receptor 4 identifies the risk of developing graft failure after liver transplantation[J].Journal of Hepatology.2010(1)
  • 9Anna Alisi,Melania Manco,Rita Devito,Fiorella Piemonte,Valerio Nobili.Endotoxin and Plasminogen Activator Inhibitor-1 Serum Levels Associated With Nonalcoholic Steatohepatitis in Children[J].Journal of Pediatric Gastroenterology and Nutrition.2010(6)
  • 10Hiroshi Kudo,Terumi Takahara,Yutaka Yata,Kengo Kawai,Wei Zhang,Toshiro Sugiyama.Lipopolysaccharide triggered TNF-α-induced hepatocyte apoptosis in a murine non-alcoholic steatohepatitis model[J].Journal of Hepatology.2009(1)

二级参考文献6

共引文献25

同被引文献615

引证文献80

二级引证文献576

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部