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

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.

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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.
Department of Internal Medicine, Division of Gastroenterology, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.
Department of Nuclear Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan.
Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Medicine, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan.
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.



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.


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


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.


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).


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.


Helicobacter pylori ; Proteobacteria; bismuth quadruple therapy; dysbiosis; microbiome

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