肠道菌群特征性改变预测儿童幽门螺杆菌治疗结果及耐药性

Characteristic changes in gut microbiota in predicting treatment outcomes and drug resistance in children with Helicobacter pylori infection

  • 摘要:
    目的 探讨儿童幽门螺杆菌(H. pylori)感染治疗前的肠道菌群特征性改变,以及分析差异菌群对治疗结果及耐药性的预测价值。
    方法 选取168例H. pylori感染患儿,均予标准四联疗法治疗14 d。按照根除疗效将患儿分为根除成功组(118例)和根除失败组(50例); 按照药敏结果分为敏感组(112例)和耐药组(56例)。采集患儿治疗前粪便样本,经16SrRNA高通量测序分析菌群多样性及组成。采用LEfSe筛选差异菌属。采用受试者工作特征(ROC)曲线评估差异菌群预测H. pylori感染患儿治疗结果及耐药性的效能。
    结果 根除失败组治疗前肠道菌群Shannon指数和Simpson指数均低于根除成功组,差异有统计学意义(P<0.001)。耐药组治疗前肠道菌群Shannon指数低于敏感组,差异有统计学意义(P<0.001)。根除成功组与根除失败组、敏感组与耐药组的菌群结构均存在显著差异(P<0.01)。根除成功组双歧杆菌属、乳杆菌属丰度高于根除失败组,敏感组的双歧杆菌属、Akkermansia属丰度高于耐药组(LDA>3.0, P<0.05)。根除失败组和耐药组的肠球菌属等条件致病菌丰度升高(LDA>3.0, P<0.05)。双歧杆菌属联合乳杆菌属预测根除成功的曲线下面积(AUC)为0.885(95%CI: 0.832~0.938); 双歧杆菌属联合Akkermansia属预测H. pylori敏感的AUC为0.912(95%CI: 0.865~0.959), 联合模型预测净获益优于单一菌属预测。
    结论 H. pylori感染患儿治疗前肠道菌群存在特征性改变,其中双歧杆菌属、乳杆菌属和Akkermansia属对治疗结果及耐药性具有良好预测价值。

     

    Abstract:
    Objective To investigate the characteristic changes in gut microbiota before treatment in children with Helicobacter pylori (H. pylori) infection, and to analyze the predictive value of differential gut microbiota for treatment outcomes and drug resistance.
    Methods A total of 168 children with H. pylori infection were enrolled and treated with standard quadruple therapy for 14 days. Based on eradication efficacy, they were divided into eradication success group (118 cases) and eradication failure group (50 cases); based on drug susceptibility results, they were divided into sensitive group (112 cases) and resistant group (56 cases). Fecal samples were collected from the children before treatment, and gut microbiota diversity and composition were analyzed using 16S rRNA high-throughput sequencing. LEfSe was employed to screen for differential bacterial genera. The receiver operating characteristic (ROC) curve was used to evaluate the performance of differential gut microbiota in predicting treatment outcomes and drug resistance in children with H. pylori infection.
    Results The Shannon index and Simpson index of gut microbiota before treatment in the eradication failure group were lower than those in the eradication success group, with statistically significant differences (P < 0.001). The Shannon index of gut microbiota before treatment in the resistant group was lower than that in the sensitive group, with statistically significant difference (P < 0.001). Significant differences in gut microbiota structure were observed between the eradication success and eradication failure groups, as well as between the sensitive and resistant groups (P < 0.01). The abundances of Bifidobacterium and Lactobacillus in the eradication success group were higher than those in the eradication failure group, while the abundances of Bifidobacterium and Akkermansia in the sensitive group were higher than those in the resistant group (LDA>3.0, P < 0.05). The abundance of opportunistic pathogenic bacteria such as Enterococcus in the eradication failure group and the drug-resistant group increased (LDA>3.0, P < 0.05). The area under the curve (AUC) for predicting eradication success using Bifidobacterium combined with Lactobacillus was 0.885 (95%CI, 0.832 to 0.938); the AUC forpredicting H. pylori sensitivity using Bifidobacterium combined with Akkermansia was 0.912 (95%CI, 0.865 to0.959). The net benefit of the combined models was superior to that of single bacterial genus prediction.
    Conclusion Characteristic changes exist in the gut microbiota of children with H. pylori infection before treatment, among which Bifidobacterium, Lactobacillus and Akkermansia demonstrate good predictive value for treatment outcomes and drug resistance.

     

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