Oral probiotic delivery-based therapeutic strategies for inflammatory bowel disease

Over the past decade, accumulating evidence supporting the efficacy of probiotics in gut microbiota modulation has spurred interest in their therapeutic potential for inflammatory bowel disease (IBD), a chronic intestinal disorder for which safer and more sustainable alternatives to conventional immunosuppressive and biologic treatments are urgently needed. Probiotics represent a promising therapeutic strategy due to their favorable biosafety profile and compatibility with daily health practices. Mechanistically, probiotics mitigate intestinal inflammation by suppressing pathogenic bacteria, modulating gut immunity and regulating microbial metabolites. However, their application is limited by low viability and poor intestinal colonization following oral administration. To address these challenges, advanced delivery strategies, including physical encapsulation, biohybrid nanocoating and chemical modifications, have been developed to enhance probiotic survival and targeted delivery. Despite these advances, current probiotic delivery systems face limitations, such as the impairment of microbial activity by surface modifications, deficiency in formulating intestinal digestion resistance strategies, lack of strategies for active colonization, and incomplete understanding of therapeutic mechanisms. By addressing these barriers, targeted and sustained research into innovative probiotic delivery systems may yield novel therapeutic approaches for IBD. This review indicates that relying solely on physical encapsulation or simple coating can no longer meet therapeutic demands. Future efforts must shift toward a functional synergy direction, developing multifunctional systems that protect probiotic viability without inhibiting their metabolic and physiological functions while integrating active colonization and targeted release. Furthermore, the review emphasizes the current incompleteness in understanding the therapeutic mechanisms of probiotics and calls for embedding mechanistic studies into the rational design of delivery systems. These insights provide a pathway for the field to move from determining whether live probiotics can be delivered to exploring how to achieve efficient, safe and functionally intact oral probiotic therapy.