Yogurt-inspired hybrid membrane vesicles for the prevention and treatment of Helicobacter pylori infection
Lujie Liu, Yiming Guo, Baikui Wang, Yuanwei Pan, Chenchen Zhao, Zhiping Xiao, Yu Liu, Guocan Yu, Xiaoyuan Chen, Lang Rao
Abstract
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.