A preliminary analysis of composition and structure of intestinal microbiota in patients with liver cirrhosis or hepatocellular carcinoma
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摘要: 目的比较分析肝硬化和肝硬化基础上发生肝细胞癌(HCC)的患者远端肠道菌群的差异,探讨肝硬化患者发生HCC与肠道菌群变化的关系。方法收集2015年12月-2016年5月天津市第三中心医院肝内科住院的慢性肝病患者35例,包括20例肝硬化患者(肝硬化组)和15例肝硬化合并HCC患者(HCC组)。收集患者粪便标本,提取其肠道细菌总DNA,采用Roche 454测序技术对16S r DNA V3-V6可变区测序,并进行生物信息分析(物种分类、丰度分析及多样性分析)。计量资料组间比较采用t检验,计数资料组间比较采用Mann-Whitney U检验。结果 20个肝硬化患者样品平均OTU为306.50±163.76,15个HCC患者样品平均OTU为357.24±168.85,2组患者OTU及alpha多样性指数相比,差异没有统计学意义(P值均>0.05)。粪便菌群序列包括的菌门主要有放线菌门(Actinobacteria)、拟杆菌门(Bacteroidetes)、厚壁菌门(Firmicutes)和变形菌门(Proteobacteria)。属种定量及组成分析发现,肝硬化组和HCC组患者肠道内多种细...Abstract: Objective To investigate the differences in intestinal microbiota between patients with liver cirrhosis and those with hepatocellular carcinoma ( HCC) complicated by liver cirrhosis, as well as the association between the change in intestinal microbiota and the development of HCC. Methods A total of 35 patients with chronic liver diseases who were hospitalized in Department of Hepatology in Tianjin Third Central Hospital from December 2015 to May 2016 were enrolled, among whom 20 patients had liver cirrhosis ( liver cirrhosis group) and 15 had HCC complicated by liver cirrhosis ( HCC group) . Fecal samples were collected from all patients, total bacterial DNA was extracted, and Roche 454 sequencing was used to determine the sequence of the V3-V6 viable regions of 16 S r DNA. A bioinformatics analysis was also performed ( species taxonomy, abundance analysis, and diversity analysis) . The t-test was used for comparison of continuous data between groups, and the Mann-Whitney U test was used for comparison of categorical data between groups. Results The mean number of operational taxonomic units ( OTUs) in the samples from the 20 liver cirrhosis patients was 306. 50 ±163. 76, and that in the samples from the 15 HCC patients was 357. 24± 168. 85; there were no significant differences in the number of OTUs and alpha diversity between the two groups of patients ( both P >0. 05) . The bacteria in fecal samples included Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. Genus-species and composition analyses showed that there was a significant difference in relative abundance of various bacteria in the intestine between the liver cirrhosis group and the HCC group, and compared with the HCC group, the liver cirrhosis group had significant increases in the proportions of Actinobacteria ( 0. 21% vs 0. 06%, U =89. 000, P =0. 043) , Bifidobacterium ( 0. 16% vs 0. 04%, U =90. 000, P =0. 046) , and Clostridium ( 0. 13% vs 0. 08%, U = 90. 000, P = 0. 046) and significant reductions in the proportions of Rikenellaceae ( 0. 58% vs 2. 30%, U = 82. 000, P = 0. 023) and Christenellaceae ( 0. 01% vs 0. 08%, U = 84. 500, P = 0. 028) . Conclusion There are significant differences in the composition of intestinal microbiota between patients with liver cirrhosis and those with HCC complicated by liver cirrhosis, while the specific mech anisms of the interaction between the differences and HCC with liver cirrhosis remained unclear.
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Key words:
- liver cirrhosis /
- carcinoma, hepatocellular /
- enterobacteriaceae
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