Role of probiotic extracellular vesicles in inter-kingdom communication and current technical limitations in advancing their therapeutic utility

Diverse functions of probiotic extracellular vesicles (EVs) have been extensively studied over the past decade, proposing their role in inter-kingdom communication. Studies have explored their therapeutic role in pathophysiological processes ranging from cancer, immunoregulation, and ulcerative colitis to stress-induced depression. These studies have highlighted the significant and novel potential of probiotic EVs for therapeutic applications, offering immense promise in addressing several unmet clinical needs. Additionally, probiotic EVs are being explored as vehicles for targeted delivery approaches. However, the realization of clinical utility of probiotic EVs is hindered by several knowledge gaps, pitfalls, limitations, and challenges, which impede their wider acceptance by the scientific community. Among these, limited knowledge of EV biogenesis, markers and regulators in bacteria, variations in cargo due to culture conditions or EV isolation method, and lack of proper understanding of gut uptake and demonstration of in vivo effect are some important issues. This review aims to summarize the diverse roles of probiotic EVs in health and disease conditions. More importantly, it discusses the significant knowledge gaps and limitations that stand in the way of the therapeutic utility of probiotic EVs. Furthermore, the importance of addressing these gaps and limitations with technical advances such as rigorous omics has been discussed.