Effect of probiotics during vonoprazan‐containing triple therapy on gut microbiota in Helicobacter pylori infection: A randomized controlled trial

Abstract

| INTRODUC TI ONHelicobacter pylori infection of the gastric epithelial mucosa affects approximately 50% of the population worldwide. In developing countries, H pylori infection has been observed in more than 90% of the population because this infection remains asymptomatic in early childhood, resulting in an enormous economic burden on healthcare resources. 1,2 Standard triple antibiotic therapy (proton-pump inhibitor (PPI) in combination with two of the following: amoxicillin, clarithromycin, or metronidazole) has been the preferred initial approach for H pylori eradication. 3 However, due to increased resistance of H pylori to clarithromycin and/or metronidazole, the eradication rate with triple therapy has reduced to <70% presently, down from >90% observed in the 1990s. 4 In Japan, decreased eradication of H pylori with the Abstract Background: Probiotics are beneficial to patients with Helicobacter pylori infections by modulating the gut microbiota. Biofermin-R (BFR) is a multiple antibiotic-resistant lactic acid bacteria preparation of Enterococcus faecium 129 BIO 3B-R and is effective in normalizing the gut microbiota when used in combination with antibiotics. This study aimed to determine the effect of BFR in combination with vonoprazan (VPZ)based therapy on gut microbiota. Methods: Patients with positive urinary anti-H pylori antibody test (primary test) and fecal H pylori antigen test (secondary test) were examined. Patients in group 1 (BFR − )received VPZ (20 mg twice daily), amoxicillin (750 mg twice daily), and clarithromycin (400 mg twice daily) for 7 days. Patients in group 2 (BFR + ) received BFR (3 tablets/ day) for 7 days, in addition to the aforementioned treatments. Following treatment, the relative abundance, α-diversity, and β-diversity of gut microbiota were assessed.Results: Supplementation with BFR prevented the decrease in α-diversity after eradication therapy (Day 7). β-diversity was similar between groups. The incidence rate of diarrhea was non-significantly higher in the BFR − than in the BFR + group (73.1% vs 56.5%; P = .361). Stool consistency was comparable in the BFR + group on Days 7 and 1 (3.86 ± 0.95 vs 3.86 ± 1.46; P = .415). Conclusion:Biofermin-R combined with VPZ-based therapy resulted in higher microbial α-strain diversity and suppressed stool softening during H pylori eradication therapy. K E Y W O R D S Biofermin-R, gut microbiota, Helicobacter pylori, vonoprazan S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Kakiuchi T, Mizoe A, Yamamoto K, et al. Effect of probiotics during vonoprazan-containing triple therapy on gut microbiota in Helicobacter pylori infection: A randomized controlled trial. Helicobacter. 2020;25:e12690.

Lack of significant differences between gastrointestinal tract microbial population structure of Helicobacter pylori‐infected subjects before and 2 years after a single eradication event

“…Alternatives to triple eradication therapy include bismuth quadruple therapy, concomitant therapy, sequential therapy, 4 and recently introduced vonoprazan therapy 58,59 . While concomitant and bismuth quadruple therapy have showed long‐term perturbations of the gut microbiome, 47 vonoprazan therapy supplemented by probiotics has been shown to improve the rate of eradication and potentially aids the maintainment of species diversity within the gut microbiome 60 . Although a number of studies have identified vonoprazan as effective eradication strategy, 59‐61 study evaluating the effect of vonoprazan monotherapy on the gut microbiome revealed stimulated lipopolysaccharide biosynthesis thus increasing the risk of enteric infection 62 .…”

“…58,59 While concomitant and bismuth quadruple therapy have showed longterm perturbations of the gut microbiome, 47 vonoprazan therapy supplemented by probiotics has been shown to improve the rate of eradication and potentially aids the maintainment of species diversity within the gut microbiome. 60 Although a number of studies have identified vonoprazan as effective eradication strategy, [59][60][61] study evaluating the effect of vonoprazan monotherapy on the gut microbiome revealed stimulated lipopolysaccharide biosynthesis thus increasing the risk of enteric infection. 62 In general, adverse events are common in combinatorial therapies, thereof vonoprazan therapy accompanied by probiotics might be promising strategy in H pylori eradication, especially in regions with high resistance rates to clarithromycin.…”

Helicobacter pylori infection and eradication: Exploring their impacts on the gastrointestinal microbiota

“…Taxonomic profiles from a metagenomic study showed a decrease in the relative abundance of Bifidobacterium after therapy 54 . The decreased Bifidobacterium was confirmed in other studies 37,50,57,60 . However, another study illustrated that Bifidobacterium increased 6 months following successful eradication 9 .…”

“…To better answer this question, recruiting negative controls is recommended in future study design. Interestingly, the proof is emerging that probiotic supplementation can alleviate the perturbation in diversity and structure caused by antibiotics 55,59,60 . Probiotics, defined as live microorganisms that can provide health benefits when consumed, have been shown to stabilize microbiota and improve gastrointestinal symptoms 31,61 .…”

Gut Microbiota Changes During Helicobacter Pylori Eradication with Vonoprazan-Containing Triple Therapy Among Adolescents: A Prospective Multicenter Study in Japan

“…To date, the safety of H. pylori eradication therapy using proton-pump inhibitor and P-CAB in children is controversial. A previous study reported the effect of probiotics during vonoprazan-containing triple therapy on the intestinal microbiota in individuals with H. pylori infection [17]. However, only the intestinal microbiota before and immediately after eradication therapy were evaluated.…”