Impact of Enterococcus faecium 129 BIO 3B-R on Helicobacter pylori eradication therapy side effects in adult patients: a randomized, double-blind, placebo-controlled study

Abstract

Managing the side effects of diarrhea, which is associated with intestinal microbial dysbiosis, is a crucial challenge in Helicobacter pylori eradication therapy. The aim of this study is to explore whether administration of a probiotic strain Enterococcus faecium 129 BIO 3B-R, a multi-antibiotic resistant lactic acid bacterium, influences the side effects of Helicobacter pylori eradication therapy in adults. Seventy-six adults undergoing this therapy were randomized to receive either Enterococcus faecium 129 BIO 3B-R or a placebo in a double-blind manner. No significant difference was observed in the incidence of diarrhea, the primary endpoint, or in any other secondary endpoints, including intestinal microbiota diversity, between two groups in the overall study population. However, in a post-hoc age-stratified analysis, participants aged 70 and older who used Enterococcus faecium 129 BIO 3B-R experienced tended to have more diarrhea during the eradication period but subsequently experienced significantly less diarrhea after eradication compared to the control group (23.1% vs. 60%). Treatment with Enterococcus faecium 129 BIO 3B-R also maintained higher α-diversity in their intestinal microbiota than those in the placebo group. Those data suggest that the administration of Enterococcus faecium 129 BIO 3B-R could potentially alleviate diarrhea and intestinal dysbiosis in over 70-year-old elderly patients undergoing Helicobacter pylori eradication.

Keywords: Helicobacter pylori; Antibiotics; Diarrhea; Intestinal microbiota; Probiotics.

Fig. 1

Flowchart and study protocol. (A) Study protocol and (B) flowchart.

Fig. 2

Comparison of intestinal microbiota and DAO activity before eradication therapy. (A) α-diversity indices in Chao1, PD whole tree, Shannon, and observed species of intestinal microbiota in the placebo group and E. faecium 129 BIO 3B-R group (3B-R group). Statistical significance was assessed using Student’s t-test. (B) Principal coordinate analysis plots with unweighted and weighted unifrac distance of intestinal microbiota before eradication therapy in the placebo and 3B-R groups. (C) Serum DAO activity between the placebo and 3B-R groups. Statistical significance was assessed using Student’s t-test. (D) FSSG score between the placebo and 3B-R groups. Statistical significance was assessed using Student’s t-test.

Fig. 3

Effect of E. faecium 129 BIO 3B-R on the incidence of diarrhea and the intestinal microbial α-diversity following antimicrobial treatment. The incidence rate of diarrhea (A) during days 1 to 7 and days 8 to 14 of eradication therapy in the placebo and 3B-R groups. P-values were obtained using the chi-squared test. (B) Intra-individual relative changes in gut microbial α-diversity during E. faecium 129 BIO 3B-R administration. For each subject, α-diversity was normalized to the pre-eradication baseline (set as 1), and the resulting relative changes are expressed as mean ± SD. P-values were calculated using two-way ANOVA tests. Comparative analysis of α-diversity in intestinal microbiota between the placebo and 3B-R groups (C) at day 7 of eradication therapy, (D) at day 14 of eradication therapy and (E) at the time of Helicobacter pylori eradication efficacy assessment. P-values were obtained using Student’s t-test.

Fig. 4

Comparison of intestinal bacterial diversity between individuals under 70 years old and those 70 years old and older before Helicobacter pylori eradication. (A) α-diversity indices in Chao, PD whole tree, Shannon, and observed species of intestinal microbiota between the younger and older subgroups before eradication therapy. *p < 0.05, **p < 0.01 by Student’s t-test. (B) Principal coordinate analysis plots with unweighted and weighted unifrac distance of intestinal microbiota before eradication therapy between the younger and older subgroups. P-values and pseudo-F were evaluated using permutational multivariate analysis of variance.

Fig. 5

Effect of E. faecium 129 BIO 3B-R on the incidence of diarrhea and the intestinal microbial α-diversity following antimicrobial treatment by age. (A) The incidence rate of diarrhea during days 1 to 7 and days 8 to 14 of eradication therapy by age in the placebo and 3B-R groups. P-values were obtained using the chi-squared test. (B) Intra-individual relative changes in gut microbial α-diversity after eradication therapy in patients aged < 70 and ≥ 70. Intra-individual relative changes in gut microbial α-diversity during E. faecium 129 BIO 3B-R administration (C) in under 70 years old and (D) in aged 70 and older. For each subject, α-diversity was normalized to the pre-eradication baseline (set as 1), and the resulting relative changes are expressed as mean ± SD. P-values were calculated using two-way ANOVA tests.