重型β地中海贫血患儿移植前后肠道菌群变化研究

doi:10.12372/jcp.2023.22e1678

Abstract

Abstract:

Objective To investigate the changes in intestinal flora in children with β-thalassemia major (β-TM) before and after hematopoietic stem cell transplantation and the influencing factors. Methods Children diagnosed with β-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 V4 region of the 16SrDNA gene. Results The study included 37 children with β-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 with β-TM was significant. The gut decontamination had little effect on the abundance of intestinal microbiota. The abundance and diversity of intestinal microbiota could not be restored in the early post-transplantation period. The selection of antibiotic types during HSCT cannot be optimized based on intestinal microbiota data.

Key words: intestinal flora, β-thalassemia major in children, hematopoietic stem cell transplantation, pediatric

WEN Jing, YU Yue, YANG Chunlan, LYU Jiayi, SONG Xinping, LI Yue, ZHANG Xiaoling, WANG Xiaodong, LIU Sixi. Changes of intestinal flora in children with β-thalassemia major before and after transplantation[J].Journal of Clinical Pediatrics, 2023, 41(11): 833-838.

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References 24

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组别	A组(n=28)	B组(n=17)	C组(n=18)	D组(n=21)	E组(n=12)	统计量	P
年龄[M(P₂₅~P₇₅)]/岁	7.3(5.0~9.9)	6.6(4.6~9.3)	7.6(6.3~10.0)	7.5(6.3~9.3)	8.2(5.9~16.6)	H=1.98	0.740
女性[n(%)]	8(28.6)	5(29.4)	5(27.8)	4(19.0)	4(33.3)	－	0.908¹⁾
供者类型[n(%)]						－	0.831¹⁾
同胞全相和	3(10.7)	4(23.5)	2(11.1)	3(14.3)	2(16.7)
无关全相和	0(0)	0(0)	1(5.6)	1(4.8)	0(0)
单倍体	25(89.0)	13(76.5)	15(83.3)	17(80.9)	10(83.3)
预处理方案[n(%)]						－	0.808¹⁾
Cy+Bu+Flu+TT+ATG	25(89.3)	13(76.5)	16(88.9)	18(85.7)	10(83.3)
Cy+CSA+Bu+Flu+TT+ATG	3(10.7)	4(23.5)	2(11.1)	3(14.3)	2(16.7)
预防GVHD[n(%)]						－	0.808¹⁾
CSA+MMF	3(10.7)	4(23.5)	2(11.1)	3(14.3)	2(16.7)
Pt-Cy+MMF+FK506	25(89.3)	13(76.5)	16(88.9)	18(85.7)	10(83.3)

组别	A组(n=28)	B组(n=17)	C组(n=18)	D组(n=21)	E组(n=12)	H值	P
厚壁菌门	40.7(24.1~50.9)	21.0(6.6~38.8)	9.9(1.1~28.2)	18.3(13.8~25.6)	48.6(20.4~92.0)	20.57	<0.001
变形菌门	73.6(2.7~15.8)	28.3(19.0~61.8)	43.6(14.3~80.8)	14.3(6.2~46.1)	3.8(0.4~54.0)	21.01	<0.001
拟杆菌门	44.5(27.8~52.8)	25.4(10.3~82.7)	0.6(0.0~39.4)	50.1(12.9~60.7)	0.4(0.1~39.0)	18.46	0.001
梭菌门	0.1(0.0~1.5)	0.1(0.0~18.7)	8.0(0.1~15.3)	0.2(0.0~20.1)	0.0(0.0~0.0)	11.22	0.024
放线菌门	0.4(0.1~13.7)	1.0(0.3~4.1)	0.0(0.0~0.1)	0.1(0.0~0.3)	0.0(0.0~0.7)	68.27	<0.001
疣状菌门	0.0(0.0~0.1)	0.0(0.0~0.1)	0.0(0.0~2.0)	0.0(0.0~0.0)	0.0(0.0~0.0)	15.41	0.040
蓝菌门	0.0(0.0~0.0)	0.0(0.0~2.7)	0.0(0.0~0.0)	0.0(0.0~0.0)	0.0(0.0~0.2)	42.65	<0.001

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

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