Helicobacter pylori is a bacterium associated with various gastrointestinal diseases of high worldwide prevalence. Since probiotics are an emerging alternative to managing infection by this pathogenic bacterium, the present work evaluated, in a randomized double-blind study controlled by a placebo, if consuming Limosilactobacillus fermentum UCO-979C prevents H. pylori infection in humans. Participants consumed either L. fermentum UCO-979C-supplemented gelatin (67 participants) or placebo-supplemented gelatin (64 participants) once a day, five days per week for 12 weeks. H. pylori infection in the participants was controlled before and after the intervention detecting H. pylori antigens in stools. Regarding H. pylori-infected participants before the study, 100% remained infected at the end of the study in the placebo group, while 96.7% of those receiving the probiotic remained infected after the intervention. Most importantly, of the non-infected participants, 34.2% became infected and 65.8% remained non-infected in the placebo group, while 2.7% became infected and 97.3% remained as non-infected individuals in the intervened group. Therefore, consuming the L. fermentum UCO-979C strain significantly reduced H. pylori infection, demonstrating a 92.6% efficacy in avoiding infection by this pathogen in non-infected individuals; thus, this probiotic is an excellent candidate to prevent H. pylori infections in non-infected individuals.

Helicobacter pylori is a cholesterol-auxotrophic pathogen capable of internalizing into Candida albicans, where the yeast may serve as a protective intracellular niche under adverse environmental conditions. Because ergosterol is an analog of cholesterol, this study investigated its contribution to the interaction between H. pylori J99 and C. albicans ATCC 90028. Ergosterol was extracted from the wild-type strain ATCC 90028 and from Δerg4, Δerg5, and Δerg6 mutants, identified and quantified by UHPLC-MS/MS, and evaluated for its effects on bacterial viability, growth, chemotaxis, and intracellular internalization. Ergosterol showed no inhibitory effect on H. pylori viability within the tested concentration range. Ergosterol extracted from C. albicans ATCC 90028 enhanced bacterial growth and induced a rapid positive chemotactic response comparable to that elicited by cholesterol, whereas ergosterol-deficient mutants produced weaker responses. Internalization assays demonstrated that reduced ergosterol availability significantly decreased bacterial entry into yeast cells. These findings identify ergosterol as a key determinant of the H. pylori–C. albicans interaction, supporting the hypothesis that fungal sterols facilitate bacterial chemotaxis and intracellular persistence. This work provides new insights into the molecular basis of bacterial–fungal endosymbiosis and suggests that ergosterol-mediated interactions may contribute to the persistence and transmission of H. pylori.