The impact of Helicobacter pylori infection, eradication therapy and probiotic supplementation on gut microenvironment homeostasis: An open-label, randomized clinical trial

Luyi Chen, Wenli Xu, Allen Lee, Jiamin He, Bixia Huang, Wenfang Zheng, Tingting Su, Sanchuan Lai, Yanqin Long, Hua Chu, Yujia Chen, Lan Wang, Kan Wang, Jianmin Si, Shujie Chen, Luyi Chen, Wenli Xu, Allen Lee, Jiamin He, Bixia Huang, Wenfang Zheng, Tingting Su, Sanchuan Lai, Yanqin Long, Hua Chu, Yujia Chen, Lan Wang, Kan Wang, Jianmin Si, Shujie Chen

Abstract

Background: Helicobacter pylori (H. pylori) infection is associated with remodeling of gastric microbiota. However, comprehensive analyses of the impact of H. pylori infection, eradication therapy and probiotic supplementation on gut microbiota are still lacking. We aimed to provide evidence for clinical decision making.

Methods: Seventy H. pylori-positive and 35 H. pylori-negative patients (group C) were enrolled. H. pylori-positive patients were randomly assigned to group A (14-day bismuth-containing quadruple therapy) and group B (quadruple therapy supplemented with Clostridium butyricum). Stool samples of group A and B were collected on day 0, 14 and 56 while stool samples of group C were collected on day 0. Gut microbiota was investigated by 16S rRNA sequencing.

Findings: The Sobs index (richness estimator) was significantly higher in H. pylori-positive samples than H. pylori-negative samples (p < .05). Several metabolic pathways were more abundant in H. pylori-positive communities while some disease-associated pathways had higher potential in H. pylori-negative community through KEGG pathway analysis. Abundances of most butyrate-producing bacteria significantly decreased, while several detrimental bacteria increased after eradication therapy. Probiotic supplementation was associated with improved gastrointestinal symptoms as well as increased Bacteroidetes:Firmicutes ratio.

Interpretation: While H. pylori infection may not be necessarily detrimental in all patients, eradication of H. pylori was associated with widespread changes in gut microbial ecology and structure. Probiotic supplementation could relieve more gastrointestinal symptoms by inducing alterations in gut microbiota and host immune responses. As such, the decision to eradicate H. pylori should be based on comprehensive analysis of individual patients.

Keywords: 16S rRNA sequencing; Bismuth-containing quadruple therapy; Clostridium butyricum; Gut microbiota; Helicobacter pylori.

Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Figures

Fig. 1
Fig. 1
Study design. BQT, bismuth-containing quadruple therapy; UBT, 13C urea breath test; GSRS, gastrointestinal symptom rating scale; BSS, Bristol stool scale.
Fig. 2
Fig. 2
Patient flowchart. BQT, bismuth-containing quadruple therapy.
Fig. 3
Fig. 3
Differences of bacterial taxa and predicted functional pathways between H. pylori-positive and H. pylori-negative groups. (A) Cladogram representation of gut microbiota taxa differences between H. pylori-positive and H. pylori-negative groups. (B) Differences of specific bacterial taxa between H. pylori-positive group and H. pylori-negative group by linear discriminant analysis (LDA) effect size (LEfSe). Red indicates taxa enriched in H. pylori-negative group and green indicates taxa enriched in H. pylori-positive group. (C, D) Pathways predicted to show significant different abundances between H. pylori-positive group and H. pylori-negative group according to Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis. *, p < .05; **, p < .01.
Fig. 4
Fig. 4
Impact of eradication therapy and probiotic supplementation on gut microbiota. (A–I) Alpha diversity indices alterations among day 0, day 14 and day 56. Sobs index (A) represents richness of community; Shannon index (B) represents diversity of community; Heip index (C) represents evenness of community. (D-G) Phyla alterations between day 0 and day 14 in group A (D) and group B (F); phyla alterations between day 0 and day 56 in group A (E) and group B (G). Bacteroidetes and Firmicutes proportions (H) and Bacteroidetes:Firmicutes (B:F) ratios (I) within different groups in different time points. *, p < .05; **, p < .01; ***, p < .001.

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