Effects of berberine-containing vs clarithromycin-containing quadruple therapy on intestinal microbiota during Helicobacter pylori eradication

doi:10.3748/wjg.122243

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastroenterol. Nov 21, 2026; 32(43): 122243
Published online Nov 21, 2026. doi: 10.3748/wjg.122243

Effects of berberine-containing vs clarithromycin-containing quadruple therapy on intestinal microbiota during Helicobacter pylori eradication

Teng-Wei Cai, Zhi-Kai Chen, Zi-Yan Lv, Wen-Jun Jiang, Ye-Yu Sun, Ling-Xiao Jin, Chen-Mei Xia, Qian-Qian Li, Xia Chen

Teng-Wei Cai, Zi-Yan Lv, Wen-Jun Jiang, Ye-Yu Sun, Ling-Xiao Jin, Qian-Qian Li, Xia Chen, Department of Gastroenterology, The First People’s Hospital of Wenling, Affiliated Wenling Hospital, Wenzhou Medical University, Wenling 317500, Zhejiang Province, China

Zhi-Kai Chen, Chen-Mei Xia, Department of Gastroenterology, The First People’s Hospital of Wenling (Taizhou University Affiliated Wenling Hospital), School of Medicine, Taizhou University, Wenling 317500, Zhejiang Province, China

Co-first authors: Teng-Wei Cai and Zhi-Kai Chen.

Author contributions: Cai TW and Chen ZK contributed equally to this work, as they are co-first authors; Cai TW and Chen ZK were involved in the study concept, design, and data collection; Jiang WJ and Chen X were involved in securing funding for the project; Lv ZY, Jiang WJ and Li QQ were involved in the interpretation of data; Sun YY, Jin LX and Xia CM were involved in the collection and analysis of data; Chen ZK, Lv ZY, Jiang WJ, Sun YY, Jin LX, Xia CM and Li QQ were involved in drafting the initial manuscript; Cai TW, Chen ZK, and Chen X were involved with the critical revision of the manuscript for important intellectual content and study supervision; all the authors have reviewed and approved the final manuscript.

AI contribution statement: Portions of this manuscript were edited using AI tools solely for language refinement. The authors carefully reviewed and verified all AI-assisted outputs and take full responsibility for the scientific content of the manuscript.

Supported by Zhejiang Provincial Science and Technology Program of Traditional Chinese Medicine, China, No. 2023ZL784; and Wenling Social Development Science and Technology Project, China, No. 2024S00303.

Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the First People’s Hospital of Wenling, Affiliated Wenling Hospital, Wenzhou Medical University (No. KY-2024-1008-01).

Clinical trial registration statement: Retrospective trial registration submitted; registration number pending official review.

Informed consent statement: All study participants, or their legal guardians, provided informed written consent prior to study enrollment.

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.

Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at werla@sina.com.

Corresponding author: Xia Chen, MD, Chief Physician, Department of Gastroenterology, The First People’s Hospital of Wenling, Affiliated Wenling Hospital, Wenzhou Medical University, No. 333 Chuan’an South Road, Chengxi Street, Wenling 317500, Zhejiang Province, China. werla@sina.com

Received: April 14, 2026
Revised: June 15, 2026
Accepted: July 13, 2026
Published online: November 21, 2026
Processing time: 166 Days and 7.2 Hours

Abstract

BACKGROUND

Helicobacter pylori (H. pylori) eradication is crucial for managing H. pylori-related gastrointestinal diseases. Berberine, a natural alkaloid, has shown potential anti-H. pylori activity, but its effectiveness and feasibility remain unclear.

AIM

To evaluate the H. pylori eradication efficacy of berberine and its impact on intestinal flora, compared with clarithromycin-based therapy.

METHODS

A total of 41 subjects with positive ¹³C-urea breath test were randomly divided into group A (berberine group) and group B (clarithromycin group). All participants underwent 14-day quadruple therapy with omeprazole 20 mg once daily, amoxicillin 0.5 g three times daily and bismuth potassium citrate 1 g four times daily; group A substituted berberine 0.3 g three times daily, whereas group B substituted berberine with clarithromycin 0.5 g twice daily. Fecal samples were collected before (A1, B1) and after (A2, B2) treatment for 16S rRNA gene sequencing to analyze intestinal flora diversity, structure, and phenotypic characteristics. H. pylori eradication efficacy was evaluated by ¹³C-urea breath test 4 weeks post-treatment.

RESULTS

The H. pylori eradication rates were 80.95% in group A and 75.00% in group B, with no statistical difference (χ² = 0.212, P = 0.719). Alpha diversity analysis showed that clarithromycin treatment (group B) significantly decreased ACE, Chao1, Sobs, and Shannon indices (all P < 0.05), while berberine treatment (group A) had no significant effect. Beta diversity and enterotype analysis revealed that clarithromycin induced significant changes in intestinal flora structure and enterotype distribution, whereas berberine maintained relatively stable flora structure. Neutral community model analysis indicated that berberine enhanced deterministic processes more significantly than clarithromycin in regulating flora assembly. Differential species analysis identified that Blautia was significantly enriched in group A post-treatment, and Dorea longicatena significantly enriched in group B.

CONCLUSION

Berberine exhibits comparable H. pylori eradication efficacy to clarithromycin, and has a milder impact on intestinal flora, maintaining flora homeostasis and reducing the risk of antibiotic resistance.

Keywords: Helicobacter pylori; Berberine; Clarithromycin; Intestinal flora; Bifidobacterium catenulatum; Blautia; Longicatena

Core Tip: This study compares berberine and clarithromycin-based therapy for Helicobacter pylori (H. pylori) eradication. The two regimens have comparable H. pylori eradication efficacy (80.95% vs 75.00%). Berberine causes milder intestinal flora disturbance, maintains flora homeostasis, enriches beneficial bacteria, and reduces antibiotic resistance risk, serving as a promising alternative for H. pylori eradication, especially in antibiotic-resistant populations.