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铋四联疗法根除幽门螺杆菌会导致肠道微生物群落失调,变形菌门相对丰度增加,拟杆菌门和放线菌门相对丰度减少。

Helicobacter pylori eradication with bismuth quadruple therapy leads to dysbiosis of gut microbiota with an increased relative abundance of Proteobacteria and decreased relative abundances of Bacteroidetes and Actinobacteria.

机构信息

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan.

Institute of Biomedical Informatics, National Yang-Ming University and Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

出版信息

Helicobacter. 2018 Aug;23(4):e12498. doi: 10.1111/hel.12498. Epub 2018 Jun 13.

DOI:10.1111/hel.12498
PMID:29897654
Abstract

BACKGROUND

Bismuth quadruple therapy is the treatment of choice for the first-line therapy of Helicobacter pylori infection in areas of high clarithromycin resistance. Currently, the impact of the promising treatment on gut microbiota remains unclear.

AIM

To investigate the short-term and long-term impacts of bismuth quadruple therapy on gut microbiota.

METHODS

Adult patients with H. pylori-related gastritis were treated with 14-day bismuth quadruple therapy. Fecal samples were collected before treatment at week 2, week 8, and week 48. Nucleic acid extraction from fecal samples was performed. The V3-V4 region of the bacterial 16S rRNA gene was amplified by polymerase chain reaction and sequenced with the MiSeq followed by data analysis using Qiime pipeline.

RESULTS

Eleven patients received complete follow-up. Before treatment, the most abundant phyla were Firmicutes (45.3%), Bacteroidetes (24.3%), Proteobacteria (9.9%), and Actinobacteria (5.0%). At the end of bismuth therapy, the relative abundances of Bacteroidetes and Actinobacteria decreased to 0.5% (P < .001) and 1.3% (P = .038), respectively. Additionally, the relative abundance of Verrucomicrobia also decreased from 3.2% to 1.11E-3% (P = .034). In contrast, the relative abundances of Proteobacteria and Cyanobacteria increased (P < .001 and P = .003, respectively). At week 8, the relative abundances of all phyla restored to the levels at baseline. The relative abundances of all phyla at week 48 also did not significantly differ from those at baseline. During eradication therapy, 6 patients (55%) reported at least 1 adverse event. The relative abundance of phylum Proteobacteria in patients with adverse effects was more than that in patients without adverse effects (68.7% ± 8.8% vs 43.4% ± 25.5%; P = .048).

CONCLUSIONS

Bismuth quadruple therapy for H. pylori eradication can lead to short-term dysbiosis of gut microbiota. The increase in Proteobacteria in gut microbiota may attribute to the development of adverse effects during bismuth quadruple therapy.

摘要

背景

铋四联疗法是克拉霉素耐药率较高地区治疗幽门螺杆菌感染的一线治疗选择。目前,这种有前途的治疗方法对肠道微生物群的影响尚不清楚。

目的

研究铋四联疗法对肠道微生物群的短期和长期影响。

方法

患有幽门螺杆菌相关性胃炎的成年患者接受 14 天铋四联疗法治疗。在治疗前、第 2 周、第 8 周和第 48 周采集粪便样本。从粪便样本中提取核酸。采用聚合酶链反应扩增细菌 16S rRNA 基因的 V3-V4 区,采用 MiSeq 进行测序,并用 Qiime 分析。

结果

11 例患者完成了完整的随访。治疗前最丰富的菌门为厚壁菌门(45.3%)、拟杆菌门(24.3%)、变形菌门(9.9%)和放线菌门(5.0%)。铋治疗结束时,拟杆菌门和放线菌门的相对丰度分别下降至 0.5%(P<0.001)和 1.3%(P=0.038)。此外,疣微菌门的相对丰度也从 3.2%下降至 1.11E-3%(P=0.034)。相反,变形菌门和蓝藻门的相对丰度增加(P<0.001 和 P=0.003)。第 8 周时,所有菌门的相对丰度均恢复至基线水平。第 48 周时,所有菌门的相对丰度与基线相比也无显著差异。在根除治疗期间,6 名患者(55%)报告至少有 1 种不良反应。有不良反应的患者的厚壁菌门相对丰度高于无不良反应的患者(68.7%±8.8%比 43.4%±25.5%;P=0.048)。

结论

铋四联疗法根除幽门螺杆菌可导致肠道微生物群短期失调。肠道微生物群中变形菌门的增加可能与铋四联疗法期间不良反应的发生有关。

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