Plant-derived extracellular vesicles for intestinal mucosal repair: mechanisms, microbiota-host interactions, and bioengineered delivery

Plant-derived extracellular vesicles (PDEVs) and related nanoparticle preparations are being investigated for intestinal mucosal repair. Much of the therapeutic evidence concerns heterogeneous plant-derived exosome-like nanoparticles (ELNs) isolated following plant tissue disruption; this review therefore distinguishes extracellularly released vesicles, tissue-derived nanoparticle preparations with unresolved origins, and reconstructed carriers. Building on foundational edible plant nanovesicle studies, we synthesize preclinical evidence across inflammatory control, structural repair, regenerative activity, and functional barrier recovery. Reported effects include modulation of macrophage activity, inflammasome signaling, and mucosal immune responses, reduced neutrophil-associated injury, epithelial protection, and improvements in junctional and mucus-associated barrier features. Intestinal stem cell responses and organoid formation support regenerative activity in selected studies, although durable regeneration remains insufficiently established. Uptake of plant-derived RNAs by gut microorganisms and metabolic relays involving tryptophan derivatives and short-chain fatty acids connect selected preparations to microbiota-host communication. Engineering strategies support drug and nucleic acid delivery, gastrointestinal protection, local colonic exposure, and cellular uptake. Evidence remains predominantly preclinical, with gaps in preparation identity, batch consistency, causal validation of active cargo, dose-exposure-response relationships, safety, and scalable manufacturing. Translation requires preparation-specific characterization and reproducible potency assays, together with integrated assessment of mucosal structure, regeneration, barrier function, and durability.