Fucoidan-modified antibiotic-free nanovesicles: A multidimensional approach to eradicate intracellular and extracellular Helicobacter pylori and restore gastrointestinal homeostasis.

Helicobacter pylori (H. pylori) infection affects nearly half of the global population, with biofilm formation and immune evasion contributing to chronic and recurrent infections, posing significant public health challenges. The robust immune evasion mechanisms and gene mutations of H. pylori not only result in a progressive decrease in clinical treatment efficacy but also increase bacterial resistance. Furthermore, antibiotic regimens have been shown to disrupt the diversity and richness of the gut microbiota. Given the challenges of eradicating H. pylori and adverse effects of antibiotics on host microbiota, this study introduces an antibiotic-free alternative strategy: fucoidan-modified kaempferol-loaded glycyrrhizic acid lipid nanovesicles (Fu-GaLip@KP). Kaempferol, supported by the nanovesicles, penetrates the mucus barrier, disperses biofilms, and eradicates bacteria. Additionally, glycyrrhetinic acid, a critical stabilizer for nanovesicles, restores lysosomal acidification and enhances the host's ability to eliminate intracellular bacteria. Notably, nanovesicles also reduce oxidative free radicals and inflammatory factor secretion, exhibiting superior efficacy in repairing gastric mucosal damage and mitigating inflammation. In vivo studies have demonstrated that Fu-GaLip@KP achieves anti-H. pylori efficacy comparable to triple therapy, while simultaneously restoring gut microbiota diversity and preventing dysbiosis. In summary, the antibiotic-free approach of Fu-GaLip@KP offers a comprehensive strategy for addressing H. pylori infection and related diseases.