儿童急性淋巴细胞白血病化疗前后肠道菌群变化特点

Changes of intestinal flora in children with acute lymphoblastic leukemia before and after chemotherapy

摘要:

目的 探索儿童急性淋巴细胞白血病（acute lymphoblastic leukemia，ALL）患儿初诊时肠道菌群的变化及化疗对肠道菌群的影响。 方法 采集40例初诊ALL患儿化疗前、化疗后2周、化疗后1个月和化疗后2个月及10例健康对照组儿童的粪便样本，进行16S rDNA测序及分析，比较ALL组与健康对照组及ALL患儿化疗前后的肠道菌群差异。 结果 与化疗前及健康对照组相比，ALL患儿化疗后1个月及2个月时肠道菌群丰度显著下降（P<0.05）。与健康对照组比较，ALL患儿化疗前后肠道菌群多样性均明显降低（P<0.05）。门水平上，放线菌门的相对丰度在ALL患儿化疗后2周、1个月及2个月时较健康对照组显著降低（P<0.05），变形菌门的相对丰度在ALL患儿化疗后1个月及2个月时较健康对照组显著升高（P<0.05）。属水平上，双歧杆菌属的相对丰度在ALL患儿化疗后2周、1个月及2个月时均较健康对照组显著降低（P<0.05）；克雷伯菌属的相对丰度在ALL患儿化疗后1个月及2个月时较健康对照组显著升高，并且在化疗后1个月时较化疗前显著升高（P<0.05）；Faecalibacterium相对丰度在ALL患儿化疗前后均较健康对照组显著降低，并且在化疗后2周及1个月时较化疗前显著降低（P<0.05）。肠球菌属相对丰度在ALL患儿化疗后1个月及2个月较健康对照组及化疗前均明显升高（P<0.05）。 结论 ALL患儿肠道菌群多样性明显低于健康儿童。化疗导致肠道菌群丰度显著降低，并可致部分有益菌（双歧杆菌属、Faecalibacterium）丰度下降、病原菌（克雷伯菌属、肠球菌属）丰度增加。 引用格式：中国当代儿科杂志，2022，24（5）：550-560

Abstract:

Objective To examine the changes of intestinal flora in children newly diagnosed with acute lymphoblastic leukemia (ALL) and the influence of chemotherapy on intestinal flora. Methods Fecal samples were collected from 40 children newly diagnosed with ALL before chemotherapy and at 2 weeks, 1 month, and 2 months after chemotherapy. Ten healthy children served as the control group. 16S rDNA sequencing and analysis were performed to compare the differences in intestinal flora between the ALL and control groups and children with ALL before and after chemotherapy. Results The ALL group had a significant reduction in the abundance of intestinal flora at 1 and 2 months after chemotherapy, with a significant reduction compared with the control group (P<0.05). Compared with the control group, the ALL group had a significant reduction in the diversity of intestinal flora before and after chemotherapy (P<0.05). At the phylum level, compared with the control group, the ALL group had a significant reduction in the relative abundance of Actinobacteria at 2 weeks, 1 month, and 2 months after chemotherapy (P<0.05) and a significant increase in the relative abundance of Proteobacteria at 1 and 2 months after chemotherapy (P<0.05). At the genus level, compared with the control group, the ALL group had a significant reduction in the relative abundance of Bifidobacterium at 2 weeks, 1 month, and 2 months after chemotherapy (P<0.05); the relative abundance of Klebsiella in the ALL group was significantly higher than that in the control group at 1 and 2 months after chemotherapy and showed a significant increase at 1 month after chemotherapy (P<0.05); the relative abundance of Faecalibacterium in the ALL group was significantly lower than that in the control group before and after chemotherapy and showed a significant reduction at 2 weeks and 1 month after chemotherapy (P<0.05). The relative abundance of Enterococcus increased significantly at 1 and 2 months after chemotherapy in the ALL group (P<0.05), and was significantly higher than that in the control group (P<0.05). Conclusions The diversity of intestinal flora in children with ALL is significantly lower than that in healthy children. Chemotherapy significantly reduces the abundance of intestinal flora and can reduce the abundance of some probiotic bacteria (Bifidobacterium and Faecalibacterium) and increase the abundance of pathogenic bacteria (Klebsiella and Enterococcus) in children with ALL. Citation:Chinese Journal of Contemporary Pediatrics, 2022, 24(5): 550-560