乙型肝炎肝硬化积证与臌胀肝肾阴虚证肠道菌群特征比较分析

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

doi:10.3969/j.issn.1001-5256.2019.04.016

乙型肝炎肝硬化积证与臌胀肝肾阴虚证肠道菌群特征比较分析

DOI: 10.3969/j.issn.1001-5256.2019.04.016

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

基金项目:

国家自然科学基金面上项目(81573948; 81874390)；

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中图分类号: R259
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- 出版日期: 2019-04-20

Features of intestinal microbiota in hepatitis B cirrhosis patients with amassment or tympanites type of liver-kidney Yin deficiency syndrome: A comparative analysis

Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine & Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine

Research funding:

摘要

摘要: 目的比较分析乙型肝炎肝硬化积证与臌胀肝肾阴虚证患者肠道菌群的分布差异。方法选取2016年10月-12月上海中医药大学附属曙光医院肝硬化科病房住院的乙型肝炎肝硬化积证（无腹水）肝肾阴虚证患者21例和臌胀（伴有腹水）肝肾阴虚证患者15例,收集患者粪便样本,提取DNA,采用16S rRNA测序技术测序,比较两者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。主成分分析采用R软件包（v.2.15.3）的ADE 4软件包,根据每个样本中的操作分类单元丰度,确定是否可以区分积证肝肾阴虚证和臌胀肝肾阴虚证。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。结果在门的水平上,与积证肝肾阴虚证组比较,臌胀肝肾阴虚证组的变形菌门的丰度显著增加(Pfdr=0.009);拟杆菌门细菌的丰度显著减少(Pfdr=0.048),放线菌门和硬壁菌门的丰度均有所减少,但2...
- 肝炎,乙型 /
- 肝硬化 /
- 肝肾阴虚 /
- 肠杆菌科
Abstract: Objective To investigate the distribution of intestinal microbiota in hepatitis B cirrhosis patients with amassment or tympanites type of liver-kidney Yin deficiency syndrome through a comparative analysis.Methods A total of 21 hepatitis B cirrhosis patients with amassment type of liver-kidney Yin deficiency syndrome (without ascites) and 15 hepatitis B cirrhosis patients with tympanites type of liver-kidney Yin deficiency syndrome (with ascites) who were treated in Department of Liver Cirrhosis, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, from October to December, 2016 were enrolled as amassment group and tympanites group, respectively.Stool samples were collected, and DNA was extracted and sequenced by 16S rRNA sequencing technology.The Wilcoxon rank-sum test was used for comparison of categorical data;The Mann-Whitney U test was used for comparison of continuous data between groups.The ADE 4 software package of R package (v.2.15.3) was used for principal component analysis, and the abundance of operational taxonomic units (OTUs) in each sample was used to determine whether the amassment and tympanites types of liver-kidney Yin deficiency syndrome could be distinguished.Multiple hypothesis tests were used for comparison of relative abundance of each species between groups and were adjusted by Benjamini and Hochberg false discovery rate (FDR) , and Pfdr<0.05 was considered statistically significant.Results Compared with the amassment group at the phylum level, the tympanites group had a significant increase in the abundance of Proteobacteria (Pfdr=0.009) and a significant reduction in the abundance of Bacteroidetes (Pfdr=0.048) , as well as slight reductions in the abundance of Actinobacteria (Pfdr>0.05) and Firmicutes (Pfdr>0.05) .Compared with the amassment group at the genus level, the tympanites group had significant increases in the abundance of Enterobacter (Pfdr=0.035) and Escherichia-Shigella (Pfdr=0.007) of the Proteobacteria phylum, as well as significant reductions in the abundance of Bifidobacterium (Pfdr=0.009) and Actinomyces (Pfdr=0.04) of the Acfinobacteria phylum and the abundance of Lachnospira (Pfdr=0.003) , Butyrivibrio (Pfdr=0.009) , Pseudobutyrivibrio (Pfdr=0.041) , Roseburia (Pfdr=0.049) , and Faecalibacterium (Pfdr=0.021) of the Firmicutes phylum.Conclusion Compared with the hepatitis B cirrhosis patients with amassment type of liver-kidney Yin deficiency syndrome, the patients with tympanites type have significant reductions in probiotic bacteria and significant increases in conditioned pathogens in intestinal microbiota, suggesting that in hepatitis B cirrhosis patients with tympanites type of liver-kidney Yin deficiency syndrome, besides liver-kidney nourishing therapy, stomach/intestine-cleansing therapy should also be adopted to regulate the imbalance of intestinal microbiota.
- hepatitis B /
- liver cirrhosis /
- LIVER-KIDNEY YIN DEFICIENCY /
- enterobacteriaceae

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参考文献(29)

[1]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.

[2]MU YP, LIU CH, LIU P. The theory of liver cirrhosis“deficiency and damage producing accumulation”:Professor Liu Ping’s academic thought[J]. Acta Univ Tradit Med Sin Pharmacol Shanghai, 2013, 27 (2) :1-4. (in Chinese) 慕永平, 刘成海, 刘平.肝硬化“虚损生积”论——刘平教授学术思想[J].上海中医药大学学报, 2013, 27 (2) :1-4.

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

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

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

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

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

[13] 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.

[14]Chinese Society of Hepatology and Chinese Society of Infectious Diseases Chinese, Medical Association. The guideline of prevention and treatment for chronic hepatitis B:A 2015 update[J]. J Clin Hepatol, 2015, 31 (12) :1941-1960. (in Chinese) 中华医学会肝病学分会, 中华医学会感染病学分会.慢性乙型肝炎防治指南 (2015年更新版) [J].临床肝胆病杂志, 2015, 31 (12) :1941-1960.

[15]Professional Committee of Digestive System Diseases, Chinese Society of Integrated Traditional Chinese and Western Medicine. Consensus on diagnosis and treatment of liver cirrhosis with integrated traditional Chinese and western medicine[J]. Chin J Integr Trad West Med Dig, 2011, 19 (4) :277-279. (in Chinese) 中国中西医结合学会消化系统疾病专业委员会.肝硬化中西医结合诊疗共识[J].中国中西医结合消化杂志, 2011, 19 (4) :277-279.

[16]ZHENG XY. Guiding principles for clinical research of new Chinese medicines[M]. Beijing:China Medical Science Press, 2002:143-148. (in Chinese) 郑筱萸.中药新药临床研究指导原则[M].北京:中国医药科技出版社, 2002:143-148.

[17]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.

[18]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 pharm therap, 2018, 47 (2) :192-202.

[19]WINTER SE, BAUMLER AJ. Why related bacterial species bloom simultaneously in the gut:Principles underlying the ‘Like wil to like’concept[J]. Cell Microbiol, 2014, 16 (2) :179-184.

[20]SHIN NR, WHON TW, BAE JW. Proteobacteria:Microbial signature of dysbiosis in gut microbiota[J]. Trends Biotechnol, 2015, 33 (9) :496-503.

[21]LITVAK Y, BYNDLOSS MX, TSOLIS RM, et al. Dysbiotic proteobacteria expansion:A microbial signature of epithelial dysfunction[J]. Curr Opin Microbiol, 2017, 39:1-6.

[22]SWIDSINSKI A, LOENING-BAUCKE V, VERSTRAELEN H, et al. Biostructure of fecal microbiota in healthy subjects and patients with chronic idiopathic diarrhea[J]. Gastroenterology, 2008, 135:568-579.

[23]RIVERA-CHAVEZ F, LOPEZ CA, BAUMLER AJ. Oxygen as a driver of gut dysbiosis[J]. Free Radic Biol Med, 2017, 105:93-101.

[24]CROXEN MA, LAW RJ, SCHOLZ R, et al. Recent advances in understanding enteric pathogenic Escherichia coli[J]. Clin Microbiol Rev, 2013, 26:822-880.

[25]CLARK DP. The fermentation pathways of Escherichia coli[J]. FEMS Microbiol Rev, 1989, 5:223-234.

[26]LIU J. Ethanol and liver:Recent insights into the mechanisms of ethanol-induced fatty liver[J]. World J Gastroenterol, 2014, 20 (40) :14672-14685.

[27]CHEN Y, GUO J, SHI D, et al. Ascitic bacterial composition is associated with clinical outcomes in cirrhotic patients with culture-negative and non-neutrocytic ascites[J]. Front Cell Infect Microbiol, 2018, 8:420.

[28]LUAN YT, CAI WJ, XU Y, et al. Role of intestinal flora in the development and progression of spontaneous bacterial peritonitis[J]. J Clin Hepatol, 2016, 32 (8) :14-17. (in Chinese) 栾雨婷, 蔡文君, 徐莹, 等.肠道菌群在自发性细菌性腹膜炎发生发展中的作用[J].临床肝胆病杂志, 2016, 32 (8) :14-17.

[29]MU YP, HU YY, LIU P. Making efforts to providing scientific evidence of therapeutic advantages of the combination of the Traditional Chinese and Western medicine in chronic hepatitis and cirrhosis[J]. J Clin Hepatol, 2015, 28 (3) :161-163. (in Chinese) 慕永平, 胡义扬, 刘平.努力为中西医结合治疗慢性肝炎肝硬化的优势提供临床科学证据[J].临床肝胆病杂志, 2015, 28 (3) :161-163.

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