Innovative probiotic Escherichia coli nissle 1917-derived outer membrane vesicles coupled microspheres demonstrate anti-inflammatory and barrier-enhancing properties in colitis

Abstract

Occurrence of inflammatory bowel disease (IBD) is increasing worldwide and has become a global health threat. Nonetheless, the effective prevention and available treatment interventions of IBD are limited. Bacterial outer membrane vesicles (OMVs) derived from probiotic bacteria such as Escherichia coli Nissle 1917 (EcN) exhibit promising anti-inflammatory, anti-oxidant, immunomodulatory, and gut microbiota modulatory functions. However, the application of OMVs in vivo encounters potential challenges due to poor tolerance against gastric juice. A delivery system of probiotic-EcN-derived OMVs was established by aldehyde-coupling to silica microspheres (SAP@OMVs) in this study. These SAP@OMVs microspheres were nontoxic to murine macrophage RAW 264.7 and human intestinal epithelial cell lines Caco-2. In the dextran sulfate sodium (DSS)-induced acute colitis models, the application of SAP@OMVs significantly improved mouse survival and alleviated the harmful effects of DSS by maintaining colon length, reducing colon injury, decreasing expression of inflammatory factors such as TNF-α and IL-1β, and increasing expression of the tight junction proteins gene zonula occludens-1 (ZO-1). The SAP@OMVs restored gut microbiota with increasing abundance of the Lactobacillus. In conclusion, the novel vehicle of OMVs demonstrated anti-inflammatory effects, representing a crucial strategy for clinical translation of OMVs as a potential therapeutic intervention for IBD.