Engineered bacterial extracellular vesicles for gastrointestinal diseases

Abstract

The gut microbiota, a complex microbial ecosystem within the gastrointestinal (GI) tract, plays a pivotal role in maintaining GI homeostasis. Dysbiosis of this community is increasingly implicated in the pathogenesis of diverse GI disorders. Bacterial extracellular vesicles (bEVs) secreted from gut microbes have emerged as an innovative therapeutic nanoplatform for GI diseases. Their unique advantages, including intrinsic biocompatibility, low immunogenicity, high drug-loading capacity, ease of customization and scalability make them a promising candidate for next-generation nanotherapies. In this review, we first discuss the biogenesis pathways, composition and internalization mechanisms of bEVs, with a particular focused on the bioactivities and mechanisms of natural bEVs in modulating gut health. Additionally, we highlight different bEVs engineering approaches to enhance bEVs functionality, stability, and disease-specific targeting, offering insights applicable to GI therapy and beyond. Despite the great potential of bEVs in various biomedical applications, challenges remain in developing standardized, scalable and reproducible bEVs production methods to facilitate clinical translation. Addressing these barriers is critical to unlocking the full therapeutic potential of bEVs in the GI disorders and other biomedical applications.