Eudragit®‐engineered pH‐responsive probiotic microspheres with enhanced gastrointestinal resistance and prolonged storage stability for inflammatory bowel disease therapy

Abstract The rising global incidence of inflammatory bowel disease (IBD) is strongly linked to gut microbiota dysbiosis driven by modern lifestyle factors, particularly dietary irregularities and antibiotic overuse. Probiotic supplementation represents a promising therapeutic strategy for microbiota modulation; specifically, Lactobacillus reuteri has been shown to improve microbial community structure, suppress colonization by pathogens, and mitigate intestinal disorders. This study introduces a hierarchically structured double‐encapsulated probiotic system, termed “core–shell” AMS@Eud, which integrates calcium alginate microspheres with a Eudragit® resin coating. This design enables pH‐responsive release and ensures superior protection of probiotic viability. After optimization, AMS@Eud demonstrated outstanding storage stability, with only 5.28% and 9.09% reduction in L. reuteri viability after 35 days at 4°C and 25°C, respectively, thereby eliminating the need for cold‐chain logistics. Under simulated gastrointestinal conditions, the system maintained a high viability of 84.60 ± 2.59% for L. reuteri , whereas free probiotics were entirely inactivated. A comprehensive bio‐safety evaluation confirmed its excellent biocompatibility and minimal hemolytic activity, with in vivo studies revealing no adverse effects on major organs. Furthermore, this platform significantly enriched beneficial gut microbes while reducing pro‐inflammatory taxa, effectively overcoming two major limitations of conventional probiotic therapy. Thus, AMS@Eud provides a transformative strategy for IBD management through precision microbiota engineering.