肝动脉化疗栓塞术后原发性肝癌患者的肠道菌群变化

李科志; 韦家康; 韩志伟; 仇雯霞; 陈欣欣; 黄山; 何剑波; 邬国斌; 陈闯

doi:10.3969/j.issn.1001-5256.2020.05.019

肝动脉化疗栓塞术后原发性肝癌患者的肠道菌群变化

DOI: 10.3969/j.issn.1001-5256.2020.05.019

1. 广西医科大学附属肿瘤医院实验研究部
2. 贵港市人民医院
3. 广西医科大学附属肿瘤医院研究生院
4. 广西医科大学第一附属医院研究生院
5. 广西医科大学附属肿瘤医院肝胆外科
6. 广西医科大学附属肿瘤医院肿瘤科
7. 广西医科大学附属肿瘤医院中医科

基金项目:

国家自然科学基金地区项目（81560726）；广西科技计划项目-重点研发计划（AB18126066）；中央引导地方科技发展专项（桂科ZY1949017）；南宁市科学研究与技术开发计划（20193116）；广西高校中青年教师科研基础能力提升项目（2020KY03048）；

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中图分类号: R735.7
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出版历程
- 出版日期: 2020-05-20

Changes in intestinal flora in patients with primary liver cancer after transcatheter arterial chemoembolization

Department of Research, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China

Research funding:

摘要

摘要:
目的对比分析原发性肝癌患者及经肝动脉化疗栓塞术（TACE）治疗前后肠道菌群的多样性变化及菌群结构差异。方法选取2018年9月-2019年1月广西医科大学附属肿瘤医院原发性肝癌患者65例（其中接受TACE治疗20例）,健康体检者27例。高通量16S rDNA测序方法分析患者便菌群结构,Anosim、LEf Se软件与R语言stats包分析菌群组间物种相对丰度、组间物种多样性、群落差异、进化分支等差异。符合正态性及方差齐的计量资料两组间比较采用t检验;不符合正态分布计量资料组间比较采用Kruskal-WallisU检验;计数资料组间比较采用χ2检验。相关性分析采取Spearman秩相关性分析。结果在门水平,各组的最大优势菌均为拟杆菌门（Bacteroidetes）、厚壁菌门（Firmicutes）,两者占比之和在健康组> 90%,在原发性肝癌组及TACE治疗组中占比均> 80%。拟杆菌门在健康组、原发性肝癌组、TACE治疗组占比分别为48. 44%、44. 96%、48. 60%,厚壁菌门在各组占比分别为47. 09%、38. 15%、33. 93%,拟杆...
- 肝肿瘤 /
- 化学栓塞,治疗性 /
- 胃肠道微生物组 /
- 物种多样性
Abstract:
Objective To investigate the changes in the diversity and structure of intestinal flora in patients with primary liver cancer after transcatheter arterial chemoembolization(TACE).Methods A total of 65 patients with primary liver cancer(among whom 20 received TACE) who were treated in The Affiliated Tumor Hospital of Guangxi Medical University from September 2018 to January 2019 were enrolled,and 27 individuals who underwent physical examination were enrolled as healthy group. High-throughput 16 S rDNA sequencing was used to analyze the structure of fecal bacterial communities, and Anosim, LEfSe software, and R language stats package were used to analyze the differences in the relative abundance, diversity, community, and evolutionary branching of intestinal flora between groups. Thet-test was used for comparison of normally distributed continuous data with homogeneity of variance between groups, and the Kruskal-WallisUtest was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. The Spearman rank correlation test was used for correlation analysis.Results At the phylum level, the dominant bacteria were Bacteroidetes and Firmicutes in each group, which accounted for > 90% in the healthy group and > 80% in the primaryliver cancer group and the TACE treatment group. Bacteroidetes accounted for 48. 44%, 44. 96%, and 48. 60%, respectively, in thehealthy group, the primary liver cancer group, and the TACE treatment group, and Firmicutes accounted for 47. 09%, 38. 15%, and33. 93%, respectively, in the three groups, suggesting that the primary liver cancer group had significantly lower relative abundance ofBacteroidetes and Firmicutes than the healthy group; in addition, the primary liver cancer group and the TACE treatment group had signifi-cantly higher relative abundance of Proteobacteria and Fusobacteria than the healthy group; although there were changes in the other phyla ofbacteria, these bacteria accounted for < 0. 5%. Compared with the primary liver cancer group, the healthy group had significantly higher a-bundance and ACE value of observed species(abundance: 264 ± 47 vs 230 ± 64,t =2.499,P= 0. 014; ACE value: 284. 11 ± 50. 82 vs252. 96 ± 67. 58,t =2.158,P= 0. 034). The rank between the primary liver cancer group and the healthy group was higher than that ineach of the two groups(R > 0), so the difference in the structure of intestinal flora between the two groups was significantly greater than thatwithin each of the two groups(P< 0. 05). The rank between the pre-TACE group and the post-TACE group was lower than that in thepre-TACE group(R < 0), so the difference in the structure of intestinal flora within the pre-TACE group and the post-TACE group wasgreater than that between the two groups(P> 0. 05). In the patients with primary liver cancer, intestinal opportunistic pathogens were cor-related with Child-Turcotte-Pugh(CTP) score, total bilirubin(TBil), alanine aminotransferase(ALT), and aspartate aminotransferase(AST)(r= 0. 245, 0. 421, 0. 327, and 0. 446,P =0. 049,P< 0. 001,P =0. 008, andP< 0. 001), and potential probiotics were corre-lated with CTP score, TBil, albumin, ALT, and AST(r=-0. 314,-0. 490, 0. 285,-0. 374, and-0. 528,P= 0. 011,P <0.001,P=0.022,P= 0. 002, andP< 0. 001). The abundance of the opportunistic pathogens among the differentially expressed bacteria increasedwith the increase in Child-Pugh class for liver function, and the patients with class C liver function had higher abundance than those withclass A or B liver function(Z =4. 301 and 4. 063,P =0. 038 and 0. 044). The relative abundance of potential probiotics tended to decreasewith the increase in Child-Pugh class for liver function, and the patients with class C liver function had lower abundance than those withclass A liver function(Z =3.882,P= 0. 049).Conclusion There are differences in the diversity and structure of intestinal flora betweenpatients with primary liver cancer and healthy individuals, and the patients with primary liver cancer have similar intestinal flora before andafter TACE, suggesting that TACE has little influence on intestinal flora. Intestinal dysbacteriosis is associated with the clinical classificationof primary liver cancer, and the degree of intestinal dysbacteriosis increases with the increase in Child-Pugh class for liver function, with areduction in potential probiotics and an increase in opportunistic pathogens.
- liver neoplasms /
- chemoembolization,therapeutic /
- gastrointestinal microbiome /
- biodiversity

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