地衣芽孢杆菌于不同时机辅助铋剂四联疗法根除幽门螺杆菌感染的疗效分析
| 作 者：姚鑫洁, 李岩, 宋函憶 |
| 单 位：中国医科大学附属盛京医院 |
| 基金项目： |
| 摘 要： |
| 背景：铋剂四联疗法根除幽门螺杆菌（Hp）感染常伴随腹泻、腹痛等不良反应，并可能破坏肠道微生态平衡，影响治疗依从性和肠道健康。联合益生菌治疗被认为是缓解这些问题的策略，但辅助使用的最佳时机尚不明确。目的：探讨于不同时机加用地衣芽孢杆菌辅助铋剂四联疗法根除Hp感染的疗效、安全性以及对肠道微生态的影响。方法：纳入2024年8月—2025年5月就诊于中国医科大学附属盛京医院消化内科门诊的150例初治Hp感染患者，随机分为铋剂四联疗法组以及同期、序贯和后期地衣芽孢杆菌组，后三组分别在14 d根除治疗的同期、同期和结束后14 d（共28 d）、结束后14 d服用地衣芽孢杆菌活菌胶囊500 mg，3次/d。评估四组患者的Hp根除率和治疗过程中的不良反应发生率，通过粪便涂片镜检和靶向培养观察根除治疗前后肠道菌群的变化。结果：四组Hp根除率意向性治疗分析和符合方案分析总体差异均无统计学意义（P均>0.05）。序贯和同期地衣芽孢杆菌组不良反应发生率低于铋剂四联疗法组（8.3%和9.4%对28.6%），但差异均无统计学意义（P均>0.008 3）。根除治疗的第14天（D14）和第28天（D28），序贯地衣芽孢杆菌组肠道菌群失调率显著低于铋剂四联疗法组（D14: 38.9%对71.4%, D28: 8.3%对48.6%, P均<0.008 3）；肠道定植抗力正常者比例显著高于铋剂四联疗法组（D14: 88.9%对60.0%, D28: 97.2%对71.4%, P均<0.008 3）。结论：地衣芽孢杆菌辅助铋剂四联疗法能减轻Hp根除治疗对肠道菌群的不良影响，促进肠道定植抗力恢复，在降低不良反应方面显示出良好的临床趋势；治疗同期与治疗后恢复期序贯给药模式效果最佳。 |
| 关键词：地衣芽孢杆菌； 幽门螺杆菌； 铋剂四联疗法； 根除率； 不良反应；肠道菌群 |
Efficacy of Different Administration Timing of Bacillus licheniformis as An Adjunct to Bismuth-containing Quadruple Therapy for Eradication of Helicobacter pylori Infection
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| Abstract: |
| Background: Bismuth-containing quadruple therapy for Helicobacter pylori (Hp) eradication is frequently associated with adverse reactions (diarrhea, abdominal pain, etc.) and may disrupt intestinal microecological homeostasis, potentially affecting treatment adherence and gut health. Probiotics supplementation is considered a strategy to mitigate these issues, but the optimal timing for adjuvant use remains unclear. Aims: To investigate the efficacy, safety, and impact on intestinal microecology of adding Bacillus licheniformis (B. licheniformis) at different time points as an adjunct to bismuth-containing quadruple therapy for Hp eradication. Methods: A total of 150 treatment-naive patients with Hp infection visited the Gastroenterology Outpatient Department, Shengjing Hospital of China Medical University from August 2024 to May 2025 were enrolled and randomly divided into four groups: bismuth-containing quadruple therapy group, as well as the concurrent, sequential, and delayed B. licheniformis groups. Patients in the latter three groups received oral B. licheniformis (500 mg, three times per day) concurrently with the 14-day eradication therapy, during the 14-day eradication therapy and continued for another 14 days (totaling 28 days), and for 14 days starting after the completion of eradication therapy, respectively. The Hp eradication rates, and the incidence of adverse reactions during the treatment course were evaluated. Changes in the gut microbiota before and after eradication therapy were observed by fecal smear microscopy and targeted culture. Results: There were no statistically significant differences in the Hp eradication rates among the four groups by intention-to-treat and per-protocol analyses (all P>0.05). Incidence rates of adverse reactions in the sequential and concurrent B. licheniformis groups were lower than those in the bismuth-containing quadruple therapy group (8.3%, and 9.4% vs. 28.6%, respectively), however, no statistically significant differences were observed (all P>0.008 3). Proportions of patients with imbalanced gut microbiota on day 14 (D14) and day 28 (D28) of eradication therapy in the sequential B. licheniformis group were significantly lower than those in the bismuth-containing quadruple therapy group (D14: 38.9% vs. 71.4%, D28: 8.3% vs. 48.6%, all P<0.008 3); while the proportions of patients with normal intestinal colonization resistance in the sequential B. licheniformis group were significantly higher than those in the bismuth-containing quadruple therapy group (D14: 88.9% vs. 60.0%, D28: 97.2% vs. 71.4%, all P<0.008 3). Conclusions: Adjuvant use of B. licheniformis with bismuth-containing quadruple therapy can reduce the adverse effects of Hp eradication therapy on gut microbiota, promote the restoration of intestinal colonization resistance, and demonstrate a favorable clinical trend in reducing adverse reactions. Sequential use of B. licheniformis (during the 14-day eradication therapy and continued for another 14 days) shows the best outcomes. |
| Keywords: Bacillus licheniformis; Helicobacter pylori; Bismuth-Containing Quadruple Therapy; Eradication Rate; Adverse Reactions; Gut Microbiota |
| 投稿时间：2025-10-24 |
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