Formyl-Peptide Receptor 2 activating probiotic Lactobacilli. Lactobacillus sp.

Probiotic bacteria like many lactobacilli help prevent or repair dysbiosis but it is largely unclear which molecules of these bacteria mediate the probiotic effects. Given the extensive crosstalk between the immune system and microbiome members, the formyl-peptide receptor 2 (FPR2) activating capacity of lactobacilli was investigated.Probiotic strains of Lactobacillus acidophilus, Lactobacillus paracasei, Lactiplantibacillus plantarum, and Lacticaseibacillus rhamnosus were isolated from probiotic products and sequenced. Calcium influx experiments in FPR1 or FPR2 overexpressing HL60 cells, and primary human neutrophils, along with pharmacological inhibition of FPR2, revealed that culture filtrates of the isolated lactobacilli strongly activate FPR2, promote killing of the methicillin resistant S. aureus USA300 and induce neutrophil chemotaxis. Pretreatment of culture filtrates with proteinase K reduced FPR2 activity, indicating that the FPR2 ligands are peptides. In silico analysis of the amphipathic properties of the signal peptides of lactic acid bacteria identified select signal peptides of L. plantarum with the ability to predominantly activate FPR2 in vitro. Thereby, via targeted activation of FPR2, peptides released by some lactobacilli are likely to positively influence the outcome of inflammatory gut diseases and could be used to treat inflammatory diseases.