A Microbial Odyssey: Reshaping Probiotic Destinies through Advanced Delivery Technologies

Probiotics have attracted considerable attention in recent years due to their potential in modulating the gut microbiota, enhancing immune function, and contributing to the management of metabolic disorders, inflammatory diseases, and neuropsychiatric conditions. However, their clinical efficacy is often compromised by harsh gastrointestinal conditions such as gastric acid, bile salts, and digestive enzymes that significantly reduce probiotic viability. Moreover, current formulations face challenges in terms of bioavailability, targeted delivery, and consistency of therapeutic outcomes. To address these limitations, a variety of delivery strategies have been developed, including colon- and inflammation-targeted systems, genetically engineered and surface-modified probiotics, microencapsulation technologies with material innovations and functional enhancements, as well as inorganic and organic nanocarrier platforms. In parallel, interdisciplinary approaches such as smart-responsive systems, biomimetic technologies, microbiota remodeling, and synthetic biology have been increasingly employed to achieve precise release and sustained colonization in the host. This review systematically summarizes recent advances in probiotic delivery technologies, covering diverse engineering strategies and material platforms. It also critically examines key challenges in clinical translation, including formulation stability, inter-individual variability, regulatory inconsistencies, and long-term safety concerns, aiming to provide a comprehensive reference for the optimization and high-quality development of probiotic delivery systems. Aiming to provide a comprehensive reference and a forward-looking framework to guide the rational design of next-generation probiotic biotherapeutics.