The Effect of Probiotics Supplementation on Gut Microbiota After Helicobacter pylori Eradication: A Multicenter Randomized Controlled Trial

Abstract

Introduction: Helicobacter pylori eradication therapy may lead to the perturbation of gut microbiota. We aim to investigate the impact of probiotics on eradication rate and gut microbiota during eradication therapy.

Methods: A total of 162 patients receiving bismuth quadruple therapy were enrolled and randomly assigned to groups given probiotics (n = 83) or placebo (n = 79) for 4 weeks. Fecal samples were collected before treatment and 2, 4, 6, and 8 weeks after eradication therapy. Gut microbiota was analyzed by 16S rRNA high-throughput sequencing.

Results: The eradication rates in the placebo and probiotics group were 82.43% and 87.01%, respectively (P > 0.05). Compared with baseline, alpha and beta diversity was significantly altered 2 weeks after eradication in both groups, which was restored at week 8. There were no significant differences in diversity between the two groups. H. pylori eradication therapy resulted in enrichment of some detrimental bacteria taxa such as Shigella, Klebsiella, and Streptococcus, while probiotics supplementation could rapidly restore these taxa levels after eradication and increase the taxa of Bacillus and Lactobacillales. Functional analysis revealed that lipopolysaccharide biosynthesis and polymyxin resistance pathways were significantly enriched after eradication, while probiotics supplementation mainly enriched the cofactors and vitamins metabolism pathways. Increased relative abundances of Roseburia and Dialister were associated with the positive eradication outcome.

Conclusions: Probiotics supplementation might help to construct a beneficial profile of gut microbiota after eradication therapy. Specific bacteria taxa are associated with H. pylori eradication outcome. These findings may be of value in rational use of probiotics during H. pylori eradication.

Trial registration: Chinese Clinical Trial Registry, ChiCTR1900022116.

Keywords: Eradication therapy; Gut microbiota; Helicobacter pylori; Probiotics.

Fig. 1

Flowchart of patient enrollment. BQT bismuth quadruple therapy

Fig. 2

Changes of alpha diversity and the comparison of diversity between the two groups. Changes in the alpha diversity before treatment and at weeks 2, 4, 6, and 8 within the placebo group (a) and probiotics group (b). Comparison of the diversity between the two groups before treatment and at weeks 2, 4, 6, and 8. Shannon (c) and observed OTU (d) indices represent the alpha diversity

Fig. 3

Comparison of the beta diversity between the two groups at different time points. Changes in the beta diversity before treatment and at weeks 2, 4, 6, and 8 within the placebo group (a) and probiotics group (b). c–f Left panel: Beta diversity (principal coordinate analysis) was compared between the two groups at week 2 (c), week 4 (d), week 6 (e), week 8 (f). Right panel: Quantification of unifrac distance

Fig. 4

Taxonomic differences in gut microbiota composition between the two groups at different time points. a Profiles of the relative abundance per group at phylum level. b Bacteroidetes to Firmicutes ratios (B:F) in the two groups at different time points. c–f Comparison of the distinct gut bacterial taxa between the placebo group and probiotics group. Bacterial taxa that are compared between the two groups at week 2 (a), week 4 (b), week 6 (c), week 8 (d) are shown by LDA score at genus levels. Taxa with P < 0.01 and LDA score > 2 were considered significant and are shown. ** P < 0.01, * P < 0.05

Fig. 5

Microbial signatures associated with eradication therapy outcome. Taxa that discriminated positive and negative eradication therapy outcomes. Relative abundances of taxa were modeled by using best subset regression. 95% confidence interval and relative abundances are shown. Y positive eradication, N negative eradication