胆汁酸的肝肠循环及肠道微生态在胆汁淤积性肝病发病和治疗中的作用

贾昊宇; 杨长青

doi:10.3969/j.issn.1001-5256.2019.02.007

胆汁酸的肝肠循环及肠道微生态在胆汁淤积性肝病发病和治疗中的作用

DOI: 10.3969/j.issn.1001-5256.2019.02.007

同济大学附属同济医院消化科

基金项目:

国家自然科学基金项目(81670571,81820108006)；

详细信息

中图分类号: R575
计量
- 文章访问数: 2126
- HTML全文浏览量: 33
- PDF下载量: 557
- 被引次数: 0
出版历程
- 出版日期: 2019-02-20

The role of enterohepatic circulation of bile acids and intestinal microbiota in the pathogenesis and treatment of cholestatic liver disease

Department of Gastroenterology, Tongji Hospital, Tongji University

Research funding:

摘要

摘要:
胆汁淤积性肝病是指由病毒、细菌、寄生虫、药物、毒物、自身免疫、酒精、结石、肿瘤和遗传代谢等一系列原因导致胆汁淤积发生而引起的肝脏疾病,主要表现为胆汁流量的改变和胆汁酸毒性的过度积累。在胆汁淤积性肝病的发病过程中,不仅有内源性胆汁酸的肝肠循环作用的参与,且肠道微生物群也通过调节代谢和免疫反应发挥重要作用。除此之外,肠道微生物群与胆汁酸的肝肠循环之间也存在密切的相互作用。胆汁酸可以改变肠道微生物群的组成,反之,肠道微生物也能够影响胆汁酸池。近年来针对胆汁酸的肝肠循环、肠道微生物群与胆汁淤积性肝病之间关系的研究日渐深入,为胆汁淤积性肝病的发病机制及治疗方法提供了一些新的研究方向。
- 胆汁淤积 /
- 胆酸类 /
- 肝肠循环 /
- 肠道微生物群
Abstract:
Cholestatic liver disease refers to a liver disorder caused by cholestasis, which arise from a series of etiologies such as viruses, bacteria, parasites, drugs, poisons, autoimmunity, alcohol, stones, tumors, genetics, and metabolism. This disease has the main manifestations of a change in bile flow and excessive accumulation of bile acid toxicity. In the pathogenesis of cholestatic liver disease, not only does the enterohepatic circulation of endogenous bile acids work, but also the intestinal microbiota plays an important role by regulating metabolism and causing immune responses. In addition, more attention has been paid to the close interaction between intestinal microbiota and the enterohepatic circulation of bile acids. Bile acids can alter the composition of intestinal microbiota, which in turn affects the bile acid pool.In recent years, there has been increasing research on the relationship of the enterohepatic circulation of bile acids and intestinal microbiota with cholestatic liver disease, which may provide new research directions for the pathogenesis and treatment of cholestatic liver disease.
- cholestasis /
- cholic acids /
- enterohepatic circulation /
- intestinal microbiota

HTML全文

参考文献(35)

[1]Chinese Society of Hepatology, Chinese Medical Association;Chinese Society of Gastroenterology, Chinese Medical Association;Chinese Society of Infectious Diseases, Chinese Medical Association.Consensus on the diagnosis and treatment of cholestasis liver diseases (2015) [J].J Clin Hepatol, 2015, 31 (12) :1989-1999. (in Chinese) 中华医学会肝病学分会, 中华医学会消化病学分会, 中华医学会感染病学分会.胆汁淤积性肝病诊断和治疗共识 (2015) [J].临床肝胆病杂志, 2015, 31 (12) :1989-1999.

[2]CAREY EJ, ALI AH, LINDOR KD.Primary biliary cirrhosis[J].Lancet, 2015, 386 (10003) :1565-1575.

[3]HIRSCHFIELD GM, KARLSEN TH, LINDOR KD, et al.Primary sclerosing cholangitis[J].Lancet, 2013, 382 (9904) :1587-1599.

[4]HORSLEY-SILVA JL, CAREY EJ, LINDOR KD.Advances in primary sclerosing cholangitis[J].Lancet Gastroenterol Hepatol, 2016, 1 (1) :68-77.

[5]LI Y, TANG R, LEUNG PSC, et al.Bile acids and intestinal microbiota in autoimmune cholestatic liver diseases[J].Autoimmun Rev, 2017, 6 (9) :885-896.

[6]LIU HX, KEANE R, SHENG L, et al.Implications of microbiota and bile acid in liver injury and regeneration[J].J Hepatol, 2015, 63 (6) :1502-1510.

[7]SCHNEIDER KM, ALBERS S, TRAUTWEIN C.Role of bile acids in the gut-liver axis[J].J Hepatol, 2018, 68 (5) :1083-1085.

[8]BEGLEY M, GAHAN CG, HILL C.The interaction between bacteria and bile[J].FEMS Microbiol Rev, 2005, 29 (4) :625-651.

[9]SPIVEY JR, BRONK SF, GORES GJ.Glycochenodeoxycholateinduced lethal hepatocellular injury in rat hepatocytes.Role of ATP depletion and cytosolic free calcium[J].J Clin Invest, 1993, 92 (1) :17-24.

[10]ALLEN K, JAESCHKE H, COPPLE BL.Bile acids induce inflammatory genes in hepatocytes:A novel mechanism of inflammation during obstructive cholestasis[J].Am J Pathol, 2011, 178 (1) :175-186.

[11]CAI SY, OUYANG X, CHEN Y, et al.Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response[J].JCI Insight, 2017, 2 (5) :e90780.

[12]O'BRIEN KM, ALLEN KM, ROCKWELL CE, et al.IL-17Asynergistically enhances bile acid-induced inflammation during obstructive cholestasis[J].Am J Pathol, 2013, 183 (5) :1498-1507.

[13] SLIJEPCEVIC D, van de GRAAF SF.Bile acid uptake transporters as targets for therapy[J].Dig Dis, 2017, 35 (3) :251-258.

[14]HOFMANN AF, HAGEY LR.Bile acids:Chemistry, pathochemistry, biology, pathobiology, and therapeutics[J].Cell Mol Life Sci, 2008, 65 (16) :2461-2483.

[15]STIEGER B, BEUERS U.The canalicular bile salt export pump BSEP (ABCB11) as a potential therapeutic target[J].Curr Drug Targets, 2011, 12 (5) :661-670.

[16]LI T, APTE U.Bile acid metabolism and signaling in cholestasis, inflammation, and cancer[J].Adv Pharmacol, 2015, 74:263-302.

[17]TRAUNER M, HALILBASIC E.Nuclear receptors as new perspective for the management of liver diseases[J].Gastroenterology, 2011, 140 (4) :1120-1125.

[18]KEITEL V, REICH M, HUSSINGER D.TGR5:Pathogenetic role and/or therapeutic target in fibrosing cholangitis[J].Clin Rev Allergy Immunol, 2015, 48 (2-3) :218-225.

[19]KEITEL V, HUSSINGER D.TGR5 in cholangiocytes[J].Curr Opin Gastroenterol, 2013, 29 (3) :299-304.

[20]CHIANG JY.Bile acid metabolism and signaling[J].Compr Physiol, 2013, 3 (3) :1191-1212.

[21]CZUL F, LEVY C.Novel therapies on primary biliary cirrhosis[J].Clin Liver Dis, 2016, 20 (1) :113-130.

[22]TRAUNER M, FUCHS CD, HALILBASIC E, et al.New therapeutic concepts in bile acid transport and signaling for management of cholestasis[J].Hepatology, 2017, 65 (4) :1393-1404.

[23]TILG H, CANI PD, MAYER EA.Gut microbiome and liver diseases[J].Gut, 2016, 65 (12) :2035-2044.

[24]TANG R, WEI Y, LI Y, et al.Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCAtherapy[J].Gut, 2018, 67 (3) :534-541.

[25]CHUNG BK, GUEVEL BT, REYNOLDS GM, et al.Phenotyping and auto-antibody production by liver-infiltrating Bcells in primary sclerosing cholangitis and primary biliary cholangitis[J].J Autoimmun, 2017, 77:45-54.

[26]MATTNER J.Impact of microbes on the pathogenesis of primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) [J].Int J Mol Sci, 2016, 17 (11) :1864.

[27]TABIBIAN JH, TALWALKAR JA, LINDOR KD.Role of the microbiota and antibiotics in primary sclerosing cholangitis[J].Biomed Res Int, 2013, 2013:389537.

[28]HALILBASIC E, FUCHS C, HOFER H, et al.Therapy of primary sclerosing cholangitis-today and tomorrow[J].Dig Dis, 2015, 33 (Suppl 2) :149-163.

[29]WOODHOUSE CA, PATEL VC, SINGANAYAGAM A, et al.Review article:The gut microbiome as a therapeutic target in the pathogenesis and treatment of chronic liver disease[J].Aliment Pharmacol Ther, 2018, 47 (2) :192-202.

[30]WATANABE M, FUKIYA S, YOKOTA A.Comprehensive evaluation of the bactericidal activities of free bile acids in the large intestine of humans and rodents[J].J Lipid Res, 2017, 58 (6) :1143-1152.

[31]JUST S, MONDOT S, ECKER J, et al.The gut microbiota drives the impact of bile acids and fat source in diet on mouse metabolism[J].Microbiome, 2018, 6 (1) :134.

[32]INAGAKI T, MOSCHETTA A, LEE YK, et al.Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor[J].Proc Natl Acad Sci U S A, 2006, 103 (10) :3920-3925.

[33]SAYIN SI, WAHLSTRM A, FELIN J, et al.Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist[J].Cell Metab, 2013, 17 (2) :225-235.

[34]KIM I, AHN SH, INAGAKI T, et al.Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine[J].J Lipid Res, 2007, 48 (12) :2664-2672.

[35]OUT C, PATANKAR JV, DOKTOROVA M, et al.Gut microbiota inhibit Asbt-dependent intestinal bile acid reabsorption via Gata4[J].J Hepatol, 2015, 63 (3) :697-704.

施引文献

资源附件(0)

访问统计