High‐Shielding and Colon‐Targeted Insect Resin Microgels for Enhanced Probiotic Viability and Colitis Alleviation

ABSTRACT The in vivo functionality of oral probiotics is often compromised by their susceptibility to environmental and gastrointestinal stressors, coupled with limited mucosal retention. To overcome these challenges, we developed a smart, pH‐responsive biomaterial platform based on shellac microgels (SCM), derived from a natural, biocompatible insect resin. Combining experimental characterization with finite element analysis, we verified that the densified molecular network of SCM functions as a potent physical barrier that effectively hinders the diffusion of O 2 , moisture, and UV radiation, as well as physiological assaults (H + and bile salts), protecting the viability of probiotics throughout storage and gastrointestinal transit. Crucially, the pK a ‐dependent phase transition of SCM enabled precise colon‐targeted bio‐interface, where its abundant functional groups facilitated strong mucosal anchoring via non‐covalent interactions. In a DSS‐induced colitis mouse model, this precision‐release strategy significantly improved therapeutic outcomes by suppressing the inflammation, restoring gut homeostasis, and repairing the epithelial barrier. This study presents a sustainable, potent, and naturally derived biomaterial strategy for the controlled delivery of sensitive bacterial therapeutics.