基于16S rDNA高通量测序研究肠道菌群与抗结核药物性肝损伤的相关性  

Study on the correlation between gut microbiota and antituberculosis drug-induced liver injury based on high-throughput sequencing of 16S rDNA

作　　者：姚琳 顾斌斌 严瑾瑜 唐佩军[1] 沈兴华[2] 张建平[1] 吴妹英[1] YAO Lin;GU Binbin;YAN Jinyu;TANG Peijun;SHEN Xinghua;ZHANG Jianping;WU Meiying(Department of Pulmonary Medicine,the Fifth People’s Hospital of Suzhou,Suzhou,Jiangsu 215131,China;Department of Critical Care Medicine,the Fifth People’s Hospital of Suzhou,Suzhou,Jiangsu 215131,China)

机构地区：[1]苏州市第五人民医院肺科,江苏苏州215131 [2]苏州市第五人民医院重症医学科,江苏苏州215131

出　　处：《临床肺科杂志》2023年第12期1803-1809,1818,共8页Journal of Clinical Pulmonary Medicine

基　　金：苏州市“科教兴卫”青年科技项目(No.KJXW2022049、No.KJXW2020048);江苏省卫生健康委重点项目(No.ZD2022041)。

摘　　要：目的探讨初治肺结核患者抗结核治疗前后肠道菌群的差异及出现药物性肝损伤时肠道菌群的变化,分析肠道菌群与抗结核药物性肝损伤(ATLI)的相关性。方法收集2020年1月至2021年1月在苏州市第五人民医院确诊的初治肺结核患者抗结核治疗前后的粪便标本,并根据患者接受抗结核药物治疗4周内是否发生肝功能异常分为肝损组(ATLI组)与对照组(Non-ATLI组),采集发生肝损伤时的粪便标本。利用实验室生化分析仪检测肝功能相关指标;通过细菌16S rDNA高通量测序法比较抗结核前后肠道菌群的多样性、物种组成及组件丰度的变化情况,采用Spearman相关系数分析差异的肠道菌属与血清肝功能指标的关系。结果两组患者抗结核治疗前后肠道菌群的丰富度,菌群组成及相对丰度差异均具有统计学意义(P<0.05);两组患者抗结核治疗前后,肠道菌群的结构均发生了改变(P<0.05);通过LEfSe分析,两组患者之间共找到17个具有显著差异的分类群(P<0.05);进一步分析肠道差异菌与肝功能指标的关系,发现乳杆菌(Lactobacillus)、Herbinix、Anaerosporobacter、[Eubacterium]brachy group、变形杆菌(Proteus)、普雷沃氏菌属9(Prevotella 9)、肠杆菌(Enterobacter)、考拉杆菌属(Phascolarctobacterium)均与肝功能指标AST、ALT存在相关性。结论肺结核患者抗结核治疗前后肠道菌群的动态变化表现出明显的差异,且差异菌属与抗结核药物性肝损伤的发生有一定的相关性。Objective To investigate the difference of intestinal flora in patients with primary treatment of pulmonary tuberculosis before and after anti-tuberculosis treatment and the changes of intestinal flora when drug-related liver injury occurs,and to analyze the correlation between intestinal flora and anti-tuberculosis drug-related liver injury(ATLI).Methods Stool specimens were collected before and after anti-tuberculosis treatment of patients with primary tuberculosis diagnosed at The Fifth People′s Hospital of Suzhou from January 2020 to January 2021,and they were divided into the liver damage group(the ATLI group)and the control group(the non-ATLI group)according to whether the patients had abnormal liver function within 4 weeks of receiving anti-tuberculosis drug treatment,and stool specimens were collected at the time of occurrence of liver damage.The liver function-related indexes were detected using a laboratory biochemical analyzer.The changes in diversity,species composition and component abundance of intestinal flora before and after anti-tuberculosis were compared by bacterial 16S rDNA high-throughput sequencing,and the relationship between differential intestinal genera and serum liver function indexes was analyzed by Spearman′s correlation coefficient.Results The differences in the abundance,flora composition and relative abundance of intestinal flora before and after anti-tuberculosis treatment were statistically significant in both groups(P<0.05).There was no significant difference in the beta diversity of intestinal flora between the ATLI and Non-ATLI groups during the same time period(P>0.05).17 taxa with significant differences were found between the two groups by LEfSe analysis(P<0.05).Further analysis of the relationship between intestinal differential bacteria and liver function indicators revealed Lactobacillus,Herbinix,Anaerosporobacter,[Eubacterium]brachy group,Proteus,Prevotella 9,Enterobacter,and Phascolarctobacterium were correlated with liver function indicators AST and ALT.Conclusio

关 键 词：肺结核 肠道菌群 抗结核药物性肝损伤 16S rDNA测序 

分 类 号：R521[医药卫生—内科学] R575[医药卫生—临床医学]