目的: 探讨幽门螺杆菌（HP）根除治疗对儿童肠道菌群结构的影响。方法: 这项横断面研究于2021年9月至2022年7月在本院进行。选择22名接受含铋四联疗法（bi-containing quadruple therapy,BQT）的幽门螺杆菌感染患儿作为BQT组,23例通过13C尿素呼气试验测试为阴性的无症状儿童被招募作为对照组。在研究前（第0周,基线时）、治疗结束时（第2周）、治疗后6周（第6周）和26周（第26周）收集粪便样本。使用基于16S rRNA基因测序对两组儿童肠道细菌组成进行分析和比较。结果: 在基线时,BQT组和对照组之间的α多样性（观察物种、Chao 1和Shannon指数）和β多样性差异无统计学意义。与基线水平相比,BQT组患者在第2周的α多样性（物种丰富度、Chao 1和Shannon指数）显著降低,并在第26周恢复到基线水平。PCoA分析显示,与基线相比,第2周BQT组（r=0.998,P=0.001）的粪便微生物群结构存在显著差异,并在第6周（r=0.051,P=0.12）和第26周（r=0.091,P=0.97）得到恢复。与基线水平相比,BQT组患者在根除后第2周的厚壁菌门[（48.23%±15.89%）vs （22.05%±11.88%）,P<0.001]和拟杆菌门[（42.99%±15.19%）vs （1.47%±2.49%）,P<0.001]的相对丰度显著降低,而变形菌门[（3.13%±3.24%）vs （74.61%±12.28）,P<0.001]的相对丰度显著增加。与基线相比,BQT组中55个细菌属的丰度发生了显著变化。其中,11个分类群显著增加,44个分类群减少。在第6周,总共87.3% （48/55）的显著改变得到恢复,在第26周,94.5% （52/55）的显著改变得到恢复。在第2周的BQT组中,几种有益分类群的相对丰度下降,包括拟杆菌属、粪大肠杆菌属、考拉杆菌属、罗氏菌属、双歧杆菌属以及经黏液真杆菌属。一些有害细菌类群的相对丰度增加,包括埃希氏菌属、克雷伯氏菌属、肠球菌属和链球菌属。结论: BQT可能导致幽门螺杆菌阳性儿童患者肠道微生物群的短暂性生态失调。这些变化在治疗26周后几乎恢复到根除前的水平。
Abstract
Objective To explore the effect of eradication therapy of Helicobacter pylori (HP) on the structure and interaction of intestinal flora in children. Methods This cross-sectional study was conducted in our hospital from September 2021 to July 2022. Twenty-two children with Helicobacter pylori infection who received bismuth-containing quadruple therapy (BQT) were selected as BQT group, and 23 asymptomatic children who passed 13C urea breath test were recruited as control group. Fecal samples were collected at 0, 2, 6 and 26 weeks. The composition of intestinal bacteria in two groups of children was analyzed and compared by sequencing based on 16S rRNA gene. Results At baseline, there was no significant difference in α diversity (observed species, Chao 1 and Shannon index) and β diversity between BQT group and control group. Compared with the baseline level, the α diversity (species richness, Chao 1 and Shannon index) of patients in BQT group decreased significantly at the second week after eradication, and returned to the baseline level at the 26th week after eradication. PCoA analysis showed that compared with the baseline, there was a significant difference in fecal microbial community structure in BQT group (r=0.998, P=0.001) at the second week, and it was recovered at the sixth week (r=0.051, P=0.12) and the 26th week (r=0.091, P=0.97). Compared with the baseline level, the relative abundance of Firmicutes [（48.23%±15.89%） vs（22.05%±11.88%）, P<0.001] and Bacteroides [（42.99%±15.19%）vs（1.47%±2.49%）, P<0.001] in BQT group decreased significantly at the second week after eradication, while the relative abundance of Proteobacteria increased significantly [（3.13%±3.24%） vs（74.61%±12.28%）, P<0.001]. Compared with the baseline, the abundance of 55 bacterial genera in BQT group changed significantly. Among them, 11 taxa increased significantly and 44 taxa decreased. In the 6th week, 87.3% (48/55) of the significant changes were restored, and in the 26th week, 94.5% (52/55) of the significant changes were restored. In the second week of BQT group, the relative abundance of several beneficial taxa decreased, including Bacteroides, fecal Escherichia, Koala, Roche, Bifidobacterium and Eubacterium myxoides. The relative abundance of some harmful bacteria groups increased, including Escherichia, Klebsiella, Enterococcus and Streptococcus. Conclusion s BQT can cause transient ecological imbalance of intestinal microflora in children with Helicobacter pylori positive. These changes almost restored to the level before eradication after 26 weeks of treatment.
关键词
儿童 /
肠道菌群 /
幽门螺杆菌 /
含铋四联疗法
Key words
children /
intestinal flora /
helicobacter pylori /
bi-containing quadruple therapy
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基金
江苏省卫生健康委员会“HP根除治疗对儿童肠道菌群结构及互作关系的影响”（20212053）
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