Lacticaseibacillus paracasei FL5 Inhibits Helicobacter pylori by Regulating Gastric Microbiota and NF-κB Signaling Pathway.

Helicobacter pylori (H. pylori) infection causes severe gastropathies, and antibiotic resistance calls for alternative therapies. In this study, Lacticaseibacillus paracasei FL5 was the most potent H. pylori antagonist, showing excellent coaggregation (97.93%), high cell surface hydrophobicity (>50%), significant urease inhibition (77.58%), and a 22.00 mm inhibition zone. In vitro, its secreted metabolites induce bacterial lysis and inhibit urease. In vivo, FL5 and IFL5 (inactivated FL5) treated H. pylori-induced gastritis, reducing H. pylori colonization, regulating oxidative stress, and repairing the mucosal barrier. They also modulated gastric microbial homeostasis and attenuated inflammation via the TLR2/MyD88/NF-κB pathway (decreased TNF-α/IL-1β/IL-6/CXCL1, increased IL-10/IL-4 and IgG). Interestingly, IFL5 demonstrated superior efficacy to live FL5 in inhibiting TLR2/NF-κB signaling, highlighting the retained immunomodulatory activity of the heat-inactivated derivative. These findings establish L. paracasei FL5 as a promising multitarget therapeutic approach.