Oral probiotics, as living therapeutics, hold considerable promise for modulating host health and preventing diseases, with substantial potential for industrial and clinical applications. However, their efficacy is substantially limited by gastrointestinal degradation and inadequate colonization, and the oversimplified linear correlation between strain survival and therapeutic efficacy, further hinder their clinical translation. This review first provides a systematic overview of current formulation approaches in oral probiotics, encompassing advanced coating techniques based on electrostatic, covalent, coordinate, bio-recognitive interactions, and synthetic biology-driven strain engineering. We emphasize the functional output of probiotic formulations as the core therapeutic driver, rather than merely structural protection. Then, the scalable manufacturing platforms including high-density fermentation and microfluidic encapsulation are summarized. The advantages and limitations of these approaches are critically assessed with regard to viability protection, targeting efficacy, industrial feasibility, and functional output for diverse diseases including colorectal cancer (CRC), inflammatory bowel disease (IBD), metabolic disorders, and neuroinflammatory conditions. Looking ahead, the convergence of multiple technological platforms is expected to drive the development of next-generation probiotic formulations. We believe that intelligently engineered oral probiotics are poised to become a safe, effective and personalized therapeutics, paving the way for their clinical adoption in precision medicine.
Liu et al. (Mon,) studied this question.