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Original research
Effect of Helicobacter pylori on gastrointestinal microbiota: a population-based study in Linqu, a high-risk area of gastric cancer
  1. Yang Guo1,
  2. Yang Zhang1,2,
  3. Markus Gerhard2,3,4,
  4. Juan-Juan Gao1,
  5. Raquel Mejias-Luque2,3,4,
  6. Lian Zhang1,
  7. Michael Vieth2,5,
  8. Jun-Ling Ma1,
  9. Monther Bajbouj2,6,
  10. Stepan Suchanek2,7,
  11. Wei-Dong Liu8,
  12. Kurt Ulm2,9,
  13. Michael Quante2,6,
  14. Zhe-Xuan Li1,2,
  15. Tong Zhou1,
  16. Roland Schmid2,6,
  17. Meinhard Classen2,6,
  18. Wen-Qing Li1,2,
  19. Wei-Cheng You1,2,
  20. Kai-Feng Pan1,2
  1. 1 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
  2. 2 PYLOTUM Key joint laboratory for upper GI cancer, Technische Universität München/Peking University Cancer Hospital & Institute, Munich/Beijing, Germany/China
  3. 3 Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany
  4. 4 German Center for Infection Research, Partner Site Munich, Munich, Germany
  5. 5 Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany
  6. 6 II. Medizinische Klinik, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany
  7. 7 Department of Medicine, 1st Faculty of Medicine, Military University Hospital, Charles University, Prague, Czech Republic
  8. 8 Linqu Public Health Bureau, Linqu, Shandong, China
  9. 9 Institute of Medical Informatics, Statistics and Epidemiology, Technische Universität München, Munich, Germany
  1. Correspondence to Dr Kai-Feng Pan, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China; pankaifeng2002{at}; Dr Wei-Cheng You, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China; weichengyou{at}


Objective Gastrointestinal microbiota may be involved in Helicobacter pylori-associated gastric cancer development. The aim of this study was to explore the possible microbial mechanisms in gastric carcinogenesis and potential dysbiosis arising from H. pylori infection.

Design Deep sequencing of the microbial 16S ribosomal RNA gene was used to investigate alterations in paired gastric biopsies and stool samples in 58 subjects with successful and 57 subjects with failed anti-H. pylori treatment, relative to 49 H. pylori negative subjects.

Results In H. pylori positive subjects, richness and Shannon indexes increased significantly (both p<0.001) after successful eradication and showed no difference to those of negative subjects (p=0.493 for richness and p=0.420 for Shannon index). Differential taxa analysis identified 18 significantly altered gastric genera after eradication. The combination of these genera into a Microbial Dysbiosis Index revealed that the dysbiotic microbiota in H. pylori positive mucosa was associated with advanced gastric lesions (chronic atrophic gastritis and intestinal metaplasia/dysplasia) and could be reversed by eradication. Strong coexcluding interactions between Helicobacter and Fusobacterium, Neisseria, Prevotella, Veillonella, Rothia were found only in advanced gastric lesion patients, and were absent in normal/superficial gastritis group. Changes in faecal microbiota included increased Bifidobacterium after successful H. pylori eradication and more upregulated drug-resistant functional orthologs after failed treatment.

Conclusion H. pylori infection contributes significantly to gastric microbial dysbiosis that may be involved in carcinogenesis. Successful H. pylori eradication potentially restores gastric microbiota to a similar status as found in uninfected individuals, and shows beneficial effects on gut microbiota.

  • helicobacter pylori - treatment
  • gastric diseases
  • gastric pre-cancer
  • bacterial interactions

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  • YG and YZ contributed equally.

  • Contributors K-FP and W-CY contributed design of the study. MB and SS conducted upper endoscopy examinations. LZ, J-LM, W-DL and Z-XL contributed to subject recruitment and sample collection. MV, KU, MQ, RS and MC completed histological diagnoses. YZ, J-JG, YG and TZ carried out experiments. YG analysed experimental results. YZ and YG wrote the draft of the manuscript. MG, RML, W-QL and K-FP revised the manuscript. All authors read and approved the submitted version.

  • Funding National Key R&D Program of China (2018YFC1313100), National Natural Science Foundation of China (81572811), International (regional) Cooperation and Exchange Project (NSFC-DFG, 81861138041), German Federal Ministry of Education and Research (BMBF) (German Research Presence in Asia: 01DO17022) to MG, German Research Foundation (DFG) (SFB 1371) to MG, Beijing Municipal Administration of Hospitals’ Ascent Plan (DFL20181102).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the Institutional Review Boards of Peking University Cancer Hospital and Institute.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as online supplementary information. The extradata about bacterial taxa are available from the responsible author for reuse under the permission of the Chinese Human Genetic Resources Administration Office.