乙型肝炎肝硬化患者伴或不伴腹水对肠道菌群的影响

栾雨婷; 蔡文君; 蒋轼丽; 赵长青; 顾宏图; 袁继丽; 邢枫; 吕靖; 刘成海; 刘平; 慕永平

doi:10.3969/j.issn.1001-5256.2020.07.015

乙型肝炎肝硬化患者伴或不伴腹水对肠道菌群的影响

DOI: 10.3969/j.issn.1001-5256.2020.07.015

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，教育部肝肾疾病重点实验室上海市中医临床重点实验室

基金项目:

国家自然科学基金面上项目资助(81573948; 81874390)；

详细信息

中图分类号: R512.62;R575.2
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出版历程
- 出版日期: 2020-07-20

A comparative study of intestinal flora between hepatitis B cirrhosis patients with or without ascites

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

Research funding:

摘要

摘要: 目的探讨乙型肝炎肝硬化（HBLC）伴有或不伴有腹水患者肠道菌群的差异。方法收集2016年10月-12月于上海中医药大学附属曙光医院肝硬化科就诊的HBLC患者57例,其中无腹水30例（HBLC-WOA）,有腹水但无SBP 27例（HBLCWA）,并纳入28例健康志愿者（HC）,采用16S rRNA测序技术,比较两组肝硬化患者间肠道菌群的分布差异。计数资料2组间比较采用Wilcoxon秩和检验;计量资料2组间比较采用Mann-Whitney U检验,3组比较采用Kruskal-Wallis H检验。组间各物种相对丰度差异的比较采用多重假设检验,采用Benjamini和Hochberg错误发现率（fdr）进行调整,Pfdr<0. 05为差异有统计学意义。相关分析采用Spearman秩相关检验。不同条件下组间的差异比较采用相似性分析（ANOSIM）和非参数多元方差分析（Adonis）。结果伴随腹水的出现,HBLC患者粪便微生物群的多样性降低（P=0. 042）。PCo A结果显示,HBLC-WOA组、HBLC-WA组与HC组间比较差异有统计学意义（HBLC-WOA vs HC,ANOSI...
- 乙型肝炎 /
- 肝硬化 /
- 腹水 /
- 胃肠道微生物组
Abstract: Objective To investigate the difference in intestinal flora between hepatitis B liver cirrhosis( HBLC) patients with or without ascites. Methods A total of 57 patients with HBLC who visited Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from October to December 2016 were enrolled,among whom 30 had no ascites( HBLC-WOA group) and 27 had ascites without spontaneous peritonitis( SBP)( HBLC-WA group),and 28 healthy volunteers were enrolled as healthy controls( HC group). Intestinal flora was compared between the two groups of HBLC patients using 16 S rRNA sequencing. The Wilcoxon rank sum test was used for comparison of categorical data between two groups,and the Mann-Whitney U test was used for comparison of continuous data between two groups;the Kruskal-Wallis H test was used for comparison of continuous variables between more than two groups. Multiple hypothesis tests were used for comparison of relative abundance between species and was adjusted by Benjamini and Hochberg false discovery rate( fdr),and Pfdr< 0. 05 was considered statistically significant. The Spearman rank correlation test was used for correlation analysis. An analysis of similarity( ANOSIM) and a non-parametric multivariate analysis of variance( Adonis) were used for comparison between groups under different conditions. Results The abundance of fecal microbiota gradually decreased with the appearance of ascites in HBLC patients( P = 0. 042).There were significant differences between the HBLC-WOA group and the HC group( ANOSIM: R = 0. 159,P = 0. 001; Adonis: R2=0. 067,P = 0. 001) and between the HBLC-WA group and the HC group( ANOSIM: R = 0. 323,P = 0. 001; Adonis: R2= 0. 107,P =0. 001). At the genus level,compared with the HC group,the HBLC-WA group had significant reductions in the abundance of Subdoligranulum and Pseudobutyrivibrio( P < 0. 01 and P < 0. 001) and significant increases in the abundance of Enterobacter,Escherichia,and Veillonella( P < 0. 05,P < 0. 001,and P < 0. 01). Escherichia and Veillonella were positively correlated with Child-Turcotte-Pugh( CTP) score,prothrombin time,and international normalized ratio and were negatively correlated with serum albumin( Alb) level( all P <0. 05). Pseudobutyrivibrio,norank ＿f ＿ Lachnospiraceae,unclassified ＿ f ＿ Lachnospiraceae,and Blautia were positively correlated with Alb level and were negatively correlated with CTP score and C-reactive protein level( all P < 0. 05). The KEGG pathway analysis showed that with the appearance of ascites,there were gradual increases in the abundance of the pathways associated with transcription-related proteins,alpha-linolenic acid metabolism,Staphylococcus aureus infection,bacterial invasion of epithelial cells,and bile secretion( all Pfdr< 0. 05),as well as a gradual reduction in the abundance of the pathway associated with the biosynthesis of flavonoids( Pfdr< 0. 05). The pathway associated with bacterial invasion of epithelial cells was positively correlated with the abundance of Escherichia( P < 0. 001),and the abundance of Enterobacter was positively correlated with the pathway of bile secretion( P < 0. 001). Conclusion Intestinal flora disturbance is observed in HBLC-WA patients,featuring the reductions in the abundance of Subdoligranulum and Pseudobutyrivibrio belonging to Firmicutes and the increases in the abundance of Enterobacter and Escherichia belonging to Proteobacteria. Enterobacter may be involved in the pathway of bile secretion,and Escherichia may be involved in the pathway associated with bacterial invasion of epithelial cells. It is suggested that regulation of intestinal flora,as well as the prophylactic treatment of SBP,should be considered for HBLC-WA patients without SBP.
- hepatitis B /
- liver cirrhosis /
- ascites /
- gastrointestinal microbiome

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参考文献(32)

[1]LU FM,ZHUANG H.Management of hepatitis B in China[J].Chin Med J(Engl),2009,122(1):3-4．

[2]WANG FS,FAN JG,ZHANG Z,et al.The global burden of liver disease:The major impact of China[J].Hepatology,2014,60(6):2099-2108．

[3]HENDRIKX T,SCHNABL B.Antimicrobial proteins:Intestinal guards to protect against liver disease[J].J Gastroenterol,2019,54(3):209-217．

[4]SENDER R,FUCHS S,MILO R.Revised estimates for the number of human and bacteria cells in the body[J].PLo S Biol,2016,14(8):e1002533．

[5]HARTMANN P,CHEN WC,SCHNABL B.The intestinal microbiome and the leaky gut as therapeutic targets in alcoholic liver disease[J].Front Physiol,2012,3:402．

[6]LIN R,ZHOU L,ZHANG J,et al.Abnormal intestinal permeability and microbiota in patients with autoimmune hepatitis[J].Int J Clin Exp Pathol,2015,8(5):5153-5160．

[7]BHAT M,ARENDT BM,BHAT V,et al.Implication of the intestinal microbiome in complications of cirrhosis[J].World J Hepatol,2016,8(27):1128-1136．

[8]GINS P,QUINTERO E,ARROYO V,et al.Compensated cirrhosis:Natural history and prognostic factors[J].Hepatology,1987,7(1):122-128．

[9]D'AMICO G,GARCIA-TSAO G,PAGLIARO L.Natural history and prognostic indicators of survival in cirrhosis:A systematic review of 118studies[J].J Hepatol,2006,44(1):217-231．

[10]van ERPECUM KJ.Ascites and spontaneous bacterial peritonitis in patients with liver cirrhosis[J].Scand J Gastroenterol Suppl,2006,243:79-84．

[11]GINS P,CRDENAS A,ARROYO V,et al.Management of cirrhosis and ascites[J].N Engl J Med,2004,350(16):1646-1654．

[12]BENTEN D,WIEST R.Gut microbiome and intestinal barrier failure-the“Achilles heel”in hepatology?[J].J Hepatol,2012,56(6):1221-1223．

[13]WIEST R,KRAG A,GERBES A.Spontaneous bacterial peritonitis:Recent guidelines and beyond[J].Gut,2012,61(2):297-310．

[14]WIEST R,GARCIA-TSAO G.Bacterial translocation(BT)in cirrhosis[J].Hepatology,2005,41(3):422-433．

[15]NOLAN JP.The role of intestinal endotoxin in liver injury:A long and evolving history[J].Hepatology,2010,52(5):1829-1835．

[16]GILL SR,POP M,DEBOY RT,et al.Metagenomic analysis of the human distal gut microbiome[J].Science,2006,312(5778):1355-1359．

[17]CHEN Y,YANG F,LU H,et al.Characterization of fecal microbial communities in patients with liver cirrhosis[J].Hepatology,2011,54(2):562-572．

[18]SANTIAGO A,POZUELO M,POCA M,et al.Alteration of the serum microbiome composition in cirrhotic patients with ascites[J].Sci Rep,2016,6:25001．

[19]KANG Y,CAI Y.Gut microbiota and hepatitis-B-virus-induced chronic liver disease:Implications for faecal microbiota transplantation therapy[J].J Hosp Infect,2017,96(4):342-348．

[20] 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．

[21]LU H,WU Z,XU W,et al.Intestinal microbiota was assessed in cirrhotic patients with hepatitis B virus infection.Intestinal microbiota of HBV cirrhotic patients[J].Microb Ecol,2011,61(3):693-703．

[22]TUOMISTO S,PESSI T,COLLIN P,et al.Changes in gut bacterial populations and their translocation into liver and ascites in alcoholic liver cirrhotics[J].BMC Gastroenterol,2014,14:40．

[23]BAJAJ JS,BETRAPALLY NS,HYLEMON PB,et al.Salivary microbiota reflects changes in gut microbiota in cirrhosis with hepatic encephalopathy[J].Hepatology,2015,62(4):1260-1271．

[24]QIN N,YANG F,LI A,et al.Alterations of the human gut microbiome in liver cirrhosis[J].Nature,2014,513(7516):59-64．

[25]WEI X,YAN X,ZOU D,et al.Abnormal fecal microbiota community and functions in patients with hepatitis B liver cirrhosis as revealed by a metagenomic approach[J].BMC Gastroenterol,2013,13:175．

[26]FAITH JJ,GURUGE JL,CHARBONNEAU M,et al.The longterm stability of the human gut microbiota[J].Science,2013,341(6141):1237439．

[27]BAJAJ JS,HEUMAN DM,HYLEMON PB,et al.Altered profile of human gut microbiome is associated with cirrhosis and its complications[J].J Hepatol,2014,60(5):940-947．

[28]BALMER ML,SLACK E,de GOTTARDI A,et al.The liver may act as a firewall mediating mutualism between the host and its gut commensal microbiota[J].Sci Transl Med,2014,6(237):237ra66．

[29]PONZIANI FR,ZOCCO MA,CERRITO L,et al.Bacterial translocation in patients with liver cirrhosis:Physiology,clinical consequences,and practical implications[J].Expert Rev Gastroenterol Hepatol,2018,12(7):641-656．

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

[31]YANG R,XU Y,DAI Z,et al.The immunologic role of gut microbiota in patients with chronic HBV infection[J].J Immunol Res,2018,2018:2361963．

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

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