Gastric microbiota composition and its association with rescue eradication outcomes in refractory Helicobacter pylori infection

Background The relationship between gastric microbiota composition, Helicobacter pylori infection, and eradication outcomes remains unclear. This study aims to explore the association of gastric microbiota composition among patients with refractory H. pylori infection with the outcomes of rescue therapy. Material and Methods Patients who failed to respond to second- or third-line eradication therapies were prospectively enrolled. The composition of the gastric microbiota was analyzed using 16S rRNA gene sequencing prior to rescue therapy. The eradication outcomes were confirmed using the [ 13 C]-urea breath test. Results Among 1,590 screened participants, 23 patients with refractory H. pylori infection who underwent rescue therapy based on antimicrobial susceptibility testing were enrolled. The alpha diversity did not differ between success and failure groups; however, the beta diversity analysis revealed a distinct microbial composition. The success group was enriched in Streptococcus , Neisseria , Cutibacterium , and Staphylococcus , with two significant species, Streptococcus mitis and Streptococcus cristatus . In contrast, Prevotella colorans was enriched in the failure group. Conclusions Distinct gastric microbiota signatures were associated with treatment outcomes in patients with refractory H. pylori infection. These findings provide insights that may facilitate the development of microbiota-based diagnostics and interventions to improve eradication success.