Probiotic-Derived Extracellular Vesicles as Potential Nano-Immunotherapeutic Platforms in IBD: A Clinician's Perspective.

Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder driven by complex interactions. Despite therapeutic advances, achieving sustained remission remains difficult, underscoring the need for safer and more durable treatment strategies. Increasing evidence highlights the pivotal role of the gut microbiota in IBD pathogenesis, prompting growing interest in microbiome-based interventions. Probiotic-derived extracellular vesicles (probiotic-derived EVs), a subset of bacterial EVs (BEVs), have emerged as promising cell-free mediators of host-microbe communication. These nanoscale vesicles can deliver bioactive cargo, modulate immune responses, and influence epithelial barrier function, thereby offering a potential strategy to regulate intestinal homeostasis while potentially avoiding some limitations associated with live microbial therapies. This review provides a comprehensive overview of probiotic-derived EVs, including their biogenesis, classification, and molecular composition. It further examines their biological functions and mechanisms of action in IBD, with a focus on barrier regulation, immune modulation, and microbial homeostasis. Recent advances in engineering strategies to enhance therapeutic efficacy are also summarized. Key challenges for clinical translation, including standardization, safety concerns, and limited clinical validation despite promising preclinical findings, are discussed. Together, these mechanistic and translational perspectives help delineate the current evidence, remaining limitations, and future directions regarding the development of probiotic-derived EVs as nanotherapeutic platforms for IBD.