From Laboratory to Real Clinical Practice: A Multidisciplinary Approach Towards the Next Probiotics

Background and Aims: Helicobacter pylori is a major cause of chronic gastritis and peptic ulcer disease. The increasing global spread of antibiotic-resistant strains, particularly against amoxicillin and clarithromycin, poses a significant challenge to eradication therapies. Moreover, treatment-related adverse effects, often linked to antibiotic-induced intestinal dysbiosis, frequently lead to a poor patient compliance; this, in turn, promotes the persistence of resistant bacterial populations. Probiotics may mitigate these effects and improve treatment adherence. This study aimed to assess the genomic safety of new probiotics intended for adjuvant use in H. pylori eradication regimens. Methods: Whole-genome sequencing was performed on three probiotic strains: one of Lactobacillus acidophilus, and two of Bifidobacterium animalis subsp. lactis. Genomes were compared with corresponding wild-type reference strains to identify genetic variations and detect mobile genetic elements. Results: Comparative genomic analysis revealed differences between selected and wild-type strains. Importantly, no plasmids or transposons were identified, suggesting a reduced theoretical risk of horizontal transfer of antimicrobial resistance determinants. Genomic findings were consistent with in vitro phenotypic observations. Conclusions: Whole-genome sequencing provided a robust assessment of the safety profile of these strains. The absence of transferable resistance elements supports their potential use as probiotic candidates to improve tolerability and adherence to H. pylori eradication therapies, contributing to more effective treatment outcomes.