中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 36 Issue 3
Mar.  2020
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Article Contents

The role of gut microbiota in the pathogenesis of portal hypertension

DOI: 10.3969/j.issn.1001-5256.2020.03.044
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  • Received Date: 2019-10-16
  • Published Date: 2020-03-20
  • Gut microbiota is the largest collection of commensal micro-organisms in the human body. Since the liver has unique anatomical location and vascular system,it is easily exposed to gut microbiota and their metabolites. Under normal conditions,the barrier function of the intestinal epithelium and the cleaning and detoxification function of the liver can prevent microorganisms or their products from entering the liver and systemic circulation. However,when the intestinal barrier function is damaged,a large number of bacterial products may enter the liver and systemic circulation and stimulate the body's immune and inflammatory responses,and such perturbations become prominent in liver cirrhosis and may increase the risk of clinically significant portal hypertension. This article summarizes the role of gut microbiota in the pathogenesis of portal hypertension and provides ideas for clinical treatment.

     

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  • [1] Chinese Society of Hepatology,Chinese Medical Association;Chinese Society of Gastroenterology,Chinese Medical Association; Chinese Society of Endoscopy,Chinese Medical Association. Guidelines for the prevention and treatment of esophageal and gastric varices bleeding in cirrhotic portal hypertension[J]. J Clin Hepatol,2016,32(2):203-219.(in Chinese)中华医学会肝病学分会,中华医学会消化病学分会,中华医学会内镜学分会.肝硬化门静脉高压食管胃静脉曲张出血的防治指南[J].临床肝胆病杂志,2016,32(2):203-219.
    [2] BAFFY G. Potential mechanisms linking gut microbiota and portal hypertension[J]. Liver Int,2019,39(4):598-609.
    [3] QIN J,LI R,RAES J,et al. A human gut microbial gene catalogue established by metagenomic sequencing[J]. Nature,2010,464(7285):59-65.
    [4] FISCHBACH MA,SONNENBURG JL. Eating for two:How metabolism establishes interspecies interactions in the gut[J].Cell Host Microbe,2011,10(4):336-347.
    [5] TILG H,CANI PD,MAYER EA. Gut microbiome and liver diseases[J]. Gut,2016,65(12):2035-2044.
    [6] YU X,WANG WJ,JIN JY,et al. Linggui Zhugan decoction combined with probiotics in the treatment of nonalcoholic fatty liver disease[J]. J Changchun Univ Chin Med,2019,35(5):891-894.(in Chinese)喻晓,王雯婕,金嘉悦,等.苓桂术甘汤联合益生菌治疗非酒精性脂肪肝[J].长春中医药大学学报,2019,35(5):891-894.
    [7] KIM YS,HO SB. Intestinal goblet cells and mucins in health and disease:Recent insights and progress[J]. Curr Gastroenterol Rep,2010,12(5):319-330.
    [8] ARAB JP,MARTIN-MATEOS RM,SHAH VH. Gut-liver axis,cirrhosis and portal hypertension:The chicken and the egg[J]. Hepatol Int,2018,12(Suppl 1):24-33.
    [9] MIYAKE Y,YAMAMOTO K. Role of gut microbiota in liver diseases[J]. Hepatol Res,2013,43(2):139-146.
    [10] KOCH M. Gut microbiota and the liver:A tale of 2 cities:A narrative view in 2 acts[J]. J Clin Gastroenterol,2016,50(Suppl 2):s183-s187.
    [11] SEO YS,SHAH VH. The role of gut-liver axis in the pathogenesis of liver cirrhosis and portal hypertension[J]. Clin Mol Hepatol,2012,18(4):337-346.
    [12] CARIELLO R,FEDERICO A,SAPONE A,et al. Intestinal permeability in patients with chronic liver diseases:Its relationship with the aetiology and the entity of liver damage[J]. Dig Liver Dis,2010,42(3):200-204.
    [13] WANG YX,LI W,CHENG DY,et al. Characteristics of intestinal flora of patients with hepatitis B related decompensated cirrhosis[J/CD]. Chin J Exp Clin Infect Dis(Electronic Version),2019,13(2):110-116.(in Chinese)王艺璇,李炜,程丹颖,等.乙型肝炎失代偿期肝硬化患者肠道菌群特征[J/CD].中华实验和临床感染病杂志(电子版),2019,13(2):110-116.
    [14] KAKIYAMA G,HYLEMON PB,ZHOU H,et al. Colonic inflammation and secondary bile acids in alcoholic cirrhosis[J]. Am J Physiol Gastrointest Liver Physiol,2014,306(11):g929-g937.
    [15] PARSÉUS A,SOMMER N,SOMMER F,et al. Microbiota-induced obesity requires farnesoid X receptor[J]. Gut,2017,66(3):429-437.
    [16] LORENZO-ZUÑIGA V,BARTOLÍR,PLANAS R,et al. Oral bile acids reduce bacterial overgrowth,bacterial translocation,and endotoxemia in cirrhotic rats[J]. Hepatology,2003,37(3):551-557.
    [17] CARIOU B,STAELS B. The expanding role of the bile acid receptor FXR in the small intestine[J]. J Hepatol,2006,44(6):1213-1215.
    [18] STALEY C,WEINGARDEN AR,KHORUTS A,et al. Interaction of gut microbiota with bile acid metabolism and its influence on disease states[J]. Appl Microbiol Biotechnol,2017,101(1):47-64.
    [19] GADALETA RM,van ERPECUM KJ,OLDENBURG B,et al.Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease[J].Gut,2011,60(4):463-472.
    [20] WAHLSTRÖM A,SAYIN SI,MARSCHALL HU,et al. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism[J]. Cell Metab,2016,24(1):41-50.
    [21] KEITEL V,REINEHR R,GATSIOS P,et al. The G-protein coupled bile salt receptor TGR5 is expressed in liver sinusoidal endothelial cells[J]. Hepatology,2007,45(3):695-704.
    [22] KELLY JR,KENNEDY PJ,CRYAN JF,et al. Breaking down the barriers:The gut microbiome,intestinal permeability and stress-related psychiatric disorders[J]. Front Cell Neurosci,2015,9:392.
    [23] ZHOU D,PAN Q,XIN FZ,et al. Sodium butyrate attenuates high-fat diet-induced steatohepatitis in mice by improving gut microbiota and gastrointestinal barrier[J]. World J Gastroenterol,2017,23(1):60-75.
    [24] CARIO E. Barrier-protective function of intestinal epithelial Toll-like receptor 2[J]. Mucosal Immunol,2008,1(Suppl1):s62-s66.
    [25] WU ZW,XU KJ,LI LJ,et al. Investigation of intestinal bacterial translocation in 78 patients with cirrhosis after liver transplantation[J]. Chin J Surg,2006,44(21):1456-1459.(in Chinese)吴仲文,徐凯进,李兰娟,等.78例肝硬化患者肠道细菌易位及其相关性研究[J].中华外科杂志,2006,44(21):1456-1459.
    [26] YU HN,LIU ZH. Recent progress in intestinal microbiota and mucosal immunity[J]. Chin J Immunol,2019,35(16):1921-1930.(in Chinese)俞昊男,刘志华.肠道微生物与黏膜免疫研究的前沿进展[J].中国免疫学杂志,2019,35(16):1921-1930.
    [27] NICHOLSON JK,HOLMES E,KINROSS J,et al. Host-gut microbiota metabolic interactions[J]. Science,2012,336(6086):1262-1267.
    [28] de FRANCHIS R. Expanding consensus in portal hypertension:Report of the Baveno VI Consensus Workshop:Stratifying risk and individualizing care for portal hypertension[J]. J Hepatol,2015,63(3):743-752.
    [29] GARCIA-TSAO G,BOSCH J. Management of varices and variceal hemorrhage in cirrhosis[J]. N Engl J Med,2010,362(9):823-832.
    [30] SENZOLO M,FRIES W,BUDA A,et al. Oral propranolol decreases intestinal permeability in patients with cirrhosis:Another protective mechanism against bleeding?[J]. Am J Gastroenterol,2009,104(12):3115-3116.
    [31] REIBERGER T,FERLITSCH A,PAYER BA,et al. Non-selective betablocker therapy decreases intestinal permeability and serum levels of LBP and IL-6 in patients with cirrhosis[J]. J Hepatol,2013,58(5):911-921.
    [32] DORON S,GORBACH SL. Probiotics:Their role in the treatment and prevention of disease[J]. Expert Rev Anti Infect Ther,2006,4(2):261-275.
    [33] GUPTA N,KUMAR A,SHARMA P,et al. Effects of the adjunctive probiotic VSL#3 on portal haemodynamics in patients with cirrhosis and large varices:A randomized trial[J]. Liver Int,2013,33(8):1148-1157.
    [34] RINCÓN D,VAQUERO J,HERNANDO A,et al. Oral probiotic VSL#3 attenuates the circulatory disturbances of patients with cirrhosis and ascites[J]. Liver Int,2014,34(10):1504-1512.
    [35] HUANG XY,LI GP,KOU JG,et al. Relationship between intestinal dysbacteriosis and Child-Pugh classification in patients with cirrhosis[J]. J Clin Hepatol,2015,31(3):392-395.(in Chinese)黄晓宇,李刚平,寇继光,等.肝硬化患者肠道菌群失调与Child-Pugh分级的关系[J].临床肝胆病杂志,2015,31(3):392-395.
    [36] KIMER N,PEDERSEN JS,BUSK TM,et al. Rifaximin has no effect on hemodynamics in decompensated cirrhosis:A randomized,double-blind,placebo-controlled trial[J]. Hepatology,2017,65(2):592-603.
    [37] LIM YL,KIM MY,JANG YO,et al. Rifaximin and propranolol combination therapy is more effective than propranolol monotherapy for the reduction of portal pressure:An open randomized controlled pilot study[J]. Gut Liver,2017,11(5):702-710.
    [38] BAJAJ JS,HEUMAN DM,SANYAL AJ,et al. Modulation of the metabiome by rifaximin in patients with cirrhosis and minimal hepatic encephalopathy[J]. PLo S One,2013,8(4):e60042.
    [39] BAJAJ JS,GILLEVET PM,PATEL NR,et al. A longitudinal systems biology analysis of lactulose withdrawal in hepatic encephalopathy[J]. Metab Brain Dis,2012,27(2):205-215.
    [40] RIGGIO O,VARRIALE M,TESTORE GP,et al. Effect of lactitol and lactulose administration on the fecal flora in cirrhotic patients[J]. J Clin Gastroenterol,1990,12(4):433-436.
    [41] MORTENSEN PB,HOLTUG K,BONNÉN H,et al. The degradation of amino acids,proteins,and blood to short-chain fatty acids in colon is prevented by lactulose[J]. Gastroenterology,1990,98(2):353-360.
    [42] RAYES N,SEEHOFER D,HANSEN S,et al. Early enteral supply of lactobacillus and fiber versus selective bowel decontamination:A controlled trial in liver transplant recipients[J].Transplantation 2002,74(1):123-127.
    [43] HALILBASIC E,FUCHS C,TRAUSSNIGG S,et al. Farnesoid X receptor agonists and other bile acid signaling strategies for treatment of liver disease[J]. Dig Dis,2016,34(5):580-588.
    [44] VERBEKE L,FARRE R,TREBICKA J,et al. Obeticholic acid,a farnesoid X receptor agonist,improves portal hypertension by two distinct pathways in cirrhotic rats[J]. Hepatology,2014,59(6):2286-2298.
    [45]'U BEDA M,LARIO M,MUNOZ L,et al. Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats[J]. J Hepatol,2016,64(5):1049-1057.
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