Long-term effects of fecal microbiota transplantation on gut microbiota after Helicobacter pylori eradication with bismuth quadruple therapy: A randomized controlled trial.

BACKGROUND: Eradicating Helicobacter pylori infection by bismuth quadruple therapy (BQT) is effective. However, the effect of BQT and subsequent fecal microbiota transplant (FMT) on the gut microbiota is less known. MATERIALS AND METHODS: This prospective randomized controlled trial was conducted at a tertiary hospital in China from January 2019 to October 2020, with the primary endpoints the effect of BQT on the gut microbiota and the effect of FMT on the gut microbiota after bismuth quadruple therapy eradication therapy. A 14-day BQT with amoxicillin and clarithromycin was administered to H. pylori-positive subjects, and after eradication therapy, patients received a one-time FMT or placebo treatment. We then collected stool samples to assess the effects of 14-day BQT and FMT on the gut microbiota. 16 s rDNA and metagenomic sequencing were used to analyze the structure and function of intestinal flora. We also used Gastrointestinal Symptom Rating Scale (GSRS) to evaluate gastrointestinal symptom during treatment. RESULTS: A total of 30 patients were recruited and 15 were assigned to either FMT or placebo groups. After eradication therapy, alpha-diversity was decreased in both groups. At the phylum level, the abundance of Bacteroidetes and Firmicutes decreased, while Proteobacteria increased. At the genus level, the abundance of beneficial bacteria decreased, while pathogenic bacteria increased. Eradication therapy reduced some resistance genes abundance while increased the resistance genes abundance linked to Escherichia coli. While they all returned to baseline by Week 10. Besides, the difference was observed in Week 10 by the diarrhea score between two groups. Compared to Week 2, the GSRS total score and diarrhea score decreased in Week 3 only in FMT group. CONCLUSIONS: The balance of intestinal flora in patients can be considerably impacted by BQT in the short term, but it has reverted back to baseline by Week 10. FMT can alleviate gastrointestinal symptoms even if there was no evidence it promoted restoration of intestinal flora.

Efficacy and safety of vonoprazan-based dual therapy and esomeprazole-based dual therapy in eradicating primary Helicobacter pylori infection: A propensity score matching analysis.

BACKGROUND: According to the Maastricht VI/Florence consensus report, potassium-competitive acid blockers (P-CAB) may improve Helicobacter pylori eradication treatment. MATERIALS AND METHODS: A total of 213 H. pylori treatment-naive patients aged between 18 and 70 years were treated with two regimens. The two regimens are VDT: 20 mg vonoprazan twice a day and 1 g amoxicillin three times daily and EDT: 20 mg esomeprazole four times a day and 750 mg amoxicillin four times daily. 13 C-urea breath tests were used to evaluate eradication rate 4-6 weeks after treatment. Based on propensity score matching (PSM), this retrospective study analyzed the eradication rates, adverse events (AEs), compliance, and antibiotic resistance rates in VDT and EDT groups. RESULTS: On intention-to-treat (ITT) analysis, the eradication rate in VDT group (89.0%; 95% CI 81.7-96.3) was non-inferior to that in EDT group (87.7%; 95% CI 80.1-95.3; p = 0.796). The corresponding per-protocol (PP) eradication rates were 94.1% (95% CI 88.4-99.8) and 92.8% (95% CI 86.7-98.9; p = 1.000), respectively. There were no significant between-group differences with respect to compliance or incidence of AEs. CONCLUSIONS: The efficacy and safety of 14-day VDT and EDT were comparable. Therefore, 14-day VDT or EDT may be recommended for the first-line treatment of H. pylori infection.

Eradication rates of Helicobacter pylori in treatment-naive patients following 14-day vonoprazan-amoxicillin dual therapy: A multicenter randomized controlled trial in China.

BACKGROUND: Potassium-competitive acid blockers (P-CAB) are recommended for the treatment of Helicobacter pylori infections, but dual therapy of P-CAB with amoxicillin has been poorly studied. The current study compared the efficacy, adverse reactions, compliance, and effects on gut microbiota of 14-day vonoprazan-amoxicillin (VA) dual therapy with esomeprazole, bismuth potassium citrate, amoxicillin, and metronidazole (EBAM) quadruple therapy in treatment-naive patients with H. pylori. MATERIALS AND METHODS: This was a multicenter, open-label, randomized, and controlled, non-inferiority study. Patients (n = 194) enrolled from six centers were randomly divided into either the VA or EBAM group. H. pylori eradication was determined using 13 C urea breath tests (UBT) 4-6 weeks post-treatment. Fecal samples were collected, and gut microbial populations were analyzed by 16S rDNA and metagenomic sequencing technology. RESULTS: Eradication rates of H. pylori in the VA and EBAM groups were 88.7% and 91.8%, respectively, according to intention-to-treat (ITT) analysis; 95.6% and 96.7% with per-protocol (PP) analysis; and 94.5% and 96.7% with modified ITT (mITT) analysis (all p > 0.05). The incidence of adverse reactions in the VA group was significantly lower compared to the EBAM group, and compliance within both groups was good. There was no difference in α-diversity or microbial composition in the VA and EBAM groups at one-month post-treatment compared to baseline, except for a markedly reduced abundance of Bacteroides in the EBAM group. CONCLUSION: VA therapy achieved excellent eradication rates with low adverse reactions, good compliance, and little impact on gut microbiota. VA therapy should be recommended as a first-line treatment against H. pylori.

High-dose dual therapy versus culture-based susceptibility-guided therapy as a rescue regimen for Helicobacter pylori infection: a randomized controlled trial.

Background: Although the Maastricht VI/Florence consensus report recommended high-dose proton pump inhibitor-amoxicillin dual therapy as possible rescue therapy for Helicobacter pylori infection, clinical evidence of its efficacy was lacking. Objectives: To compare the efficacy, safety, patient compliance, and cost between high-dose dual therapy (HDDT) and culture-based susceptibility-guided therapy (CB-SGT) as a rescue regimen for H. pylori infection. Design: A single-center, open-label, randomized controlled clinical trial. Methods: In all, 146 patients with a history of eradication failure were enrolled and randomly assigned to receive HDDT or CB-SGT. HDDT consisted of esomeprazole 20 mg and amoxicillin 750 mg, both given four times per day (qid). CB-SGT consisted of esomeprazole 20 mg twice daily (bid), amoxicillin 1000 mg bid plus clarithromycin 500 mg bid, metronidazole 400 mg bid, or levofloxacin 500 mg daily (qd) for sensitive patients, in that order. For patients with triple resistance, a bismuth-containing regimen with a high dose of metronidazole was chosen, including esomeprazole 20 mg bid, bismuth 220 mg bid, amoxicillin 1000 mg bid, and metronidazole 400 mg qid. All regimens were given for 14 days. Results: The eradication H. pylori rates achieved with HDDT in the intention-to-treat (ITT), per-protocol, and modified ITT analyses were all 84.9% [62/73, 95% confidence interval (CI): 76.5-93.9%], compared with 83.6% (61/73, 95% CI: 74.9-92.3%), 84.7% (61/72, 95% CI: 76.2-93.2%), and 84.7% (61/72, 95% CI: 76.2-93.2%) with CB-SGT, respectively. For patients with CYP2C19 polymorphisms of intermediate/poor metabolizers, the eradication rates of HDDT and CB-SGT were 90.70% (39/43, 95% CI: 77.86-97.41%) and 84.21% (32/38, 95% CI: 68.75-93.98%), respectively. The difference between groups was 6.49% (95% CI: -8.00% to 20.97%), and the non-inferiority p value was 0.0128. For patients with a treatment interval of more than 3 months, the eradication rates of the two regimens reached 88.71% (95% CI: 78.11-95.34%) and 71.97% (95% CI: 70.02-90.64%). The difference between groups was 6.74% (95% CI: -5.71% to 19.20%), with a non-inferiority p value of 0.0042. Patient adherence was high in both groups. The HDDT had a lower cost and rate of side effects (p < 0.001) compared with CB-SGT. Conclusions: HDDT can reach an eradication rate of 85% in treatment-experienced patients of H. pylori infection and 91% in patients with CYP2C19 polymorphisms of intermediate/poor metabolizers, with good compliance, lower side effects and costs, and less use of antibiotics. In conclusion, HDDT offers an effective rescue regimen for H. pylori infection. Registration: This clinical trial was registered at the Chinese Clinical Trail Registry (trail registration number: ChiCTR1900025044).

Efficacy and safety of high-dose esomeprazole and amoxicillin dual therapy versus bismuth-containing quadruple therapy for Helicobacter pylori infection: a multicenter, randomized controlled clinical trial.

Background: A high-dose proton pump inhibitor (PPI)-amoxicillin dual therapy has been investigated for treatment of patients with Helicobacter pylori (H. pylori) infection. Currently, the efficacy of this dual therapy remains inconclusive, with controversial findings from various single-center clinical trials. Objectives: To assess the efficacy and safety of high-dose dual therapy (HDDT) compared with the bismuth-containing quadruple therapy (BQT) in treatment-naive patients with H. pylori infection. Design: A multicenter, open-label, randomized controlled clinical trial. Methods: Three hundred and forty treatment-naïve patients with H. pylori infection were prospectively recruited from seven participating hospitals. The enrolled patients were randomized into one of two treatment groups: the HDDT group (esomeprazole, 20 mg four times daily; amoxicillin, 750 mg four times daily) and the BQT group (esomeprazole, 20 mg, twice daily; bismuth potassium citrate, 600 mg, twice daily; amoxicillin, 1 g, twice daily; metronidazole, 400 mg, four times daily). The primary outcome was eradication rate, and secondary outcomes were safety and patient compliance. Results: The eradication rates in the HDDT group versus the BQT group were 86.47% versus 87.06% on intention-to-treat (ITT) analysis, 91.88% versus 92.50% on modified ITT (MITT) analysis, and 91.77% versus 93.04% on per-protocol (PP) analysis, with no significant differences between the two groups. The patient compliance rates in the HDDT group versus the BQT group were 97.02% versus 95.86%, and no significant difference was found between the two groups. Notably, the HDDT group exhibited significantly lower incidence in the drug-induced adverse events (AEs) compared to the BQT group (16.67% versus 47.94%). Conclusion: HDDT is equally efficacious in eradicating H. pylori infection and resulted in good patient compliance and safety compared with BQT. These findings provide evidence in support of HDDT as a first-line treatment for H. pylori infection. Registration: This clinical trial was registered at The Chinese Clinical Trial Registry (trial registration number: ChiCTR2000039096).