Impact of Probiotic-Adjunctive Vonoprazan-Amoxicillin Dual Therapy on Gut Microbiota and Clinical Symptoms in Helicobacter pylori Eradication.

Background: This study evaluates the impact of Bacillus subtilis dual-strain enteric-coated capsules combined with vonoprazan-amoxicillin (VA) therapy on Helicobacter pylori (Hp) eradication rates, gastrointestinal symptoms, adverse events (AEs), and gut microbiota.

Methods: 60 Hp-positive adults were enrolled, allocated to probiotic (n = 30) or placebo (n = 30) groups. Both groups received a 14-day VA dual therapy, with the probiotic group additionally receiving a 28-day Bacillus subtilis dual-strain capsule regimen and the placebo group receiving matched placebos. Outcomes included Hp eradication rates (intention-to-treat [ITT]/per-protocol [PP] analyses), Gastrointestinal Symptom Rating Scale (GSRS) scores, AEs, antibiotic susceptibility, and gut microbiota changes (16S rRNA sequencing).

Results: ITT analysis showed identical eradication rates (93.33%) in both groups; PP analysis revealed 96.67% (probiotic) versus 93.33% (placebo). The probiotic group exhibited significantly lower GSRS scores at weeks 4 (T2) and 8 (T3), particularly for diarrhea and acid reflux, with milder AEs (severity score: 5). Probiotic supplementation reduced Hp resistance to metronidazole (26.67% vs. 60.00%) without affecting other antibiotics. Microbiota analysis demonstrated post-eradication reductions in gastric pathogens (e.g., Helicobacter) and increased beneficial bacteria (e.g., Lactobacillus). The probiotic group showed faster restoration of gut α-diversity (higher at T2), enriched butyrate producers (e.g., Blautia, Anaerobutyricum), and decreased opportunistic pathogens (e.g., Klebsiella).

Conclusions: Although Bacillus subtilis supplementation did not enhance Hp eradication rates, it significantly improved gastrointestinal symptoms, reduced AEs, increased Hp susceptibility to metronidazole, and accelerated microbiota recovery, supporting its role in microbiome modulation during Hp eradication therapy.