"Cocktail-style" probiotic co-delivery system a multi-component strategy to overcome gastrointestinal challenges.

Although current probiotics encapsulation strategies greatly improve survival in the gastrointestinal tract, they still face challenges adapting to its complex and dynamic physicochemical environment. Accordingly, this study draws on "cocktail therapy" to develop a multi-component protection oral delivery system. The core consists of carboxymethyl gellan gum (CMGG)/pectin (CP) microspheres loaded with Bifidobacterium (Bif), sequentially coated with pectin and sodium alginate (SA) using chitosan (CS) as an adhesive, followed by a mineralized calcium carbonate (CaCO₃) outer layer. In this system, the CaCO₃ layer neutralizes gastric acid and offers physical protection, while the pH-responsive SA layer degrades in the intestine to release the core. The inner CP and CS layer enhances structural stability and enables colon-targeted release; in the core, CP and CMGG form a composite gel network that acts as a prebiotic, supporting bacterial growth and enabling a self-sustaining system. Carboxymethylation of CMGG improves mucosal adhesion and inflammation targeting, facilitating Bif colonization in the colon. In summary, this multi-component protection delivery system significantly enhances probiotic stability and targeted colonization during the delivery process through a combination of physical barriers, chemical responsiveness, and nutritional support. Further investigations revealed that Bif@CMPS@CaCO₃ was effective in restoring gut microbiota balance and thereby enhancing intestinal health.