重型β地中海贫血患儿移植前后肠道菌群变化研究  

Changes of intestinal flora in children withβ-thalassemia major before and after transplantation

作　　者：闻静 余阅 杨春兰[1] 吕佳忆 宋欣平 李越[1] 张小玲[1] 王晓东[1] 刘四喜[1] WEN Jing;YU Yue;YANG Chunlan;LYU Jiayi;SONG Xinping;LI Yue;ZHANG Xiaoling;WANG Xiaodong;LIU Sixi(Shenzhen Children’s Hospital,Shenzhen 518038,Guangdong,China;China Medical University Shenzhen Children’s Hospital,Shenzhen 518038,Guangdong,China)

机构地区：[1]深圳市儿童医院血液肿瘤科,广东深圳518038 [2]中国医科大学深圳市儿童医院,广东深圳518038

出　　处：《临床儿科杂志》2023年第11期833-838,共6页Journal of Clinical Pediatrics

基　　金：广东省高水平临床重点专科(深圳市配套建设经费)(No.SZGSP012);深圳市医学重点学科建设经费资助(No.SZXK034)。

摘　　要：目的了解重型β地中海贫血(β-TM)患儿造血干细胞移植前后不同阶段肠道菌群改变及其影响因素。方法选择2019年11月至2020年6月在血液肿瘤科行造血干细胞移植的确诊β-TM的患儿作为研究对象。收集移植启动前期(A组)、清洁肠道期(B组)、预处理期(C组)、干细胞输注期(D组)及移植后细胞植入期(E组)的粪便样本。利用16SrDNA基因V4区域的Illumina HiSeq测序系统测序粪便样本。结果纳入37例β-TM患儿,男27例、女10例,中位年龄7.5(3.0~17.3)岁。最终纳入分析共96份样本,A组28份、B组17份、C组18份、D组21份、E组12份。A组和B组肠道菌群构成占比前两位为厚壁菌门、拟杆菌门,C、D、E组菌群占比前两位为变形菌门及拟杆菌门。5组之间厚壁菌门、变形菌门、拟杆菌门、梭菌门、放线菌门、疣状菌门、蓝菌门的丰度差异均有统计学意义(P<0.05)。利用Chao指数比较移植不同时期肠道菌群Alpha丰度。A组Chao指数为225.9(182.0~260.5),B组为234.6(193.0~311.3),C组为127.6(81.1~180.0),D组为96.8(71.1~139.9),E组为122.7(97.5~142.7),5组之间差异有统计学意义(P<0.001)。利用Shannon指数预测移肠道菌群Alpha多样性。A组Shannon指数为2.9(2.4~3.3),B组为2.2(1.6~2.9)、C组为1.4(1.2~2.0)、D组为2.0(1.4~2.3)、E组为0.9(0.6~2.2),5组之间差异有统计学意义(P<0.001)。万古霉素、亚胺培南-西司他丁以及其他类型广谱抗菌药物三组之间肠道菌群丰度与多样性差异无统计学意义(P>0.05)。结论造血干细胞移植术对β-TM患儿肠道菌群的组成有较大影响;清洁肠道方案对肠道菌群的丰度影响不大;肠道菌群丰度及多样性在移植后早期不能恢复重建;在造血干细胞移植过程中暂无法依据肠道菌群来优化选择抗生素种类。Objective To investigate the changes in intestinal flora in children withβ-thalassemia major(β-TM)before and after hematopoietic stem cell transplantation and the influencing factors.Methods Children diagnosed withβ-TM who underwent HSCT from November 2019 to June 2020 were enrolled as the research subjects.Fecal samples were collected during the pre-transplantation stage(group A),gut decontamination period(group B),conditioning period(group C),hematopoietic stem cell infusion period(group D),and post-transplantation cellular implantation period(group E).The fecal samples were sequenced using Illumina HiSeq sequencing system targeting the V 4 region of the 16 SrDNA gene.Results The study included 37 children withβ-TM,including 27 males and 10 females with a median age of 7.5(3.0-17.3)years.A total of 96 samples were analyzed,with 28 from group A,17 from group B,18 from group C,21 from group D,and 12 from group E.The two most abundant phyla in groups A and B were Firmicutes and Bacteroidetes.In contrast,the two most abundant phyla in groups C,D,and E were Proteobacteria and Bacteroidetes.The differences in the abundances of Firmicutes,Proteobacteria,Bacteroidetes,Actinobacteria,Cyanobacteria,Verrucomicrobia,and Fusobacteria among the five groups were statistically significant(P<0.05).The Chao was used to compare the alpha diversity of intestinal flora at different transplantation stages.The differences among the five groups were statistically significant(P<0.001).Similarly,the Shannon was used to predict alpha diversity of intestinal flora,and the differences among the five groups were also statistically significant(P<0.001).There were no statistically significant differences in the abundance and diversity of intestinal flora among the three groups treated with vancomycin,imipenem-cilastatin,and other broad-spectrum antibiotics(P>0.05).Conclusions The effect of hematopoietic stem cell transplantation on the composition of intestinal flora in children withβ-TM was significant.The gut decontamination had little

关 键 词：肠道菌群 重型Β地中海贫血 造血干细胞移植 儿童 

分 类 号：R725.5[医药卫生—儿科]