Novel anti-virulence strategy against Helicobacter pylori using Lactiplantibacillus plantarum cell-free supernatants

Résumé

Helicobacter pylori is one of the most prevalent pathogenic microorganisms worldwide. The treatment of H. pylori infections is challenging due to the increasing antibiotic resistance. Therefore, alternative therapies are crucial for addressing these issues. This study aimed to investigate alternative approaches to combat H. pylori infection using lactic acid bacteria. Nineteen LAB isolates exhibited strong tolerance to simulated gastric acid and bile salts, as well as notable auto-aggregation and co-aggregation capabilities. Among them, isolates L20, L22, and L40 showed superior performance. Their neutralized cell-free supernatants (n-CFSs) significantly inhibited H. pylori urease production by 69, 66, and 67%, respectively, and reduced biofilm formation by 88, 82, and 80%, respectively. Molecular identification revealed that isolates L20 and L40 belonged to Lactiplantibacillus plantarum , while L22 was identified as Limosilactobacillus fermentum . Furthermore, the n-CFS of L. plantarum L20 markedly downregulated the expression of H. pylori virulence genes, including vacA , cagA , ureA , and babA, with fold reductions of 79, 68, 90, and 96%, respectively. In vivo , treatment with L. plantarum L20 n-CFS resulted in 1.28 log reduction in H. pylori colonization ( p < 0.001). Proteomic analysis further identified metabolically active proteins associated with catalytic and secondary metabolite pathways, supporting their mechanistic role in anti- H. pylori activity. These findings highlight the potential of LAB-derived n-CFS, particularly L. plantarum L20, as a promising antivirulent strategy against H. pylori infections.

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