Yogurt-inspired hybrid membrane vesicles for the prevention and treatment of Helicobacter pylori infection

Helicobacter pylori ( H. pylori ) infection is a critical initiating factor in numerous gastrointestinal diseases. Here, we present yogurt-inspired hybrid membrane vesicles (hMVs) engineered by fusing bacterial outer membrane vesicles (OMVs) with modified milk fat globule membrane vesicles (MMVs) to prevent and treat H. pylori infection. The hMVs function as binding site competitors, reducing bacterial adhesion while regulating epithelial integrity and immune responses. This dual mechanism synergistically inhibits H. pylori infection and promotes gastric epithelial repair. In vitro , hMVs demonstrated remarkable efficacy in accelerating scratch-wound healing, enhancing lipid raft formation, increasing tight junction protein ZO-1 expression, and promoting macrophage phagocytosis of apoptotic epithelial cells. In mouse models for both H. pylori prevention and treatment, oral administration of hMVs effectively reduced H. pylori loads by 86% and 66%, respectively. Additionally, this treatment mitigated inflammatory factor secretion, decreased neutrophil recruitment, and preserved the abundance of beneficial probiotics in the stomach. • Bioinspired hMVs serve as a non-antibiotic strategy to inhibit H. pylori infection • hMVs enhance epithelial integrity by upregulating lipid rafts and ZO-1 expression • hMVs mitigate inflammation by reducing cytokine secretion and neutrophil recruitment • hMVs exert the potential of maintaining the abundance of gut-healthy probiotics H. pylori infection affects more than 50% of the global population. Conventional antibiotic regimens for treating H. pylori infection face challenges such as antibiotic resistance and are ineffective in repairing the damaged gastric mucosal barrier and maintaining gastric microecological homeostasis. Here, we developed yogurt-inspired hybrid membrane vesicles (hMVs) for the prevention and treatment of H. pylori infection. The hMVs demonstrated excellent properties in repairing the damaged gastric mucosal barrier and reducing H. pylori adhesion to the gastric mucosa. These effects included enhancing lipid raft formation and tight junction protein ZO-1 expression, reducing inflammatory factor secretion and neutrophil recruitment, and preserving the abundance of beneficial probiotics in the stomach. This bioinspired nanocomplex provides a simple, safe, and effective antibiotic-independent strategy to combat pathogen infection while maintaining gastrointestinal homeostasis. Liu et al. developed yogurt-inspired hybrid membrane vesicles (hMVs) for the prevention and treatment of H. pylori infection as an antibiotic-free approach. The hMVs exhibited excellent properties in repairing gastric mucosal barrier damage following H. pylori infection and effectively reducing H. pylori adhesion. This work introduces an anti-infection paradigm where hMVs simultaneously repair gastric mucosal damage and inhibit bacterial colonization.