A Probiotic‐Derived Oral Dual‐Triggered Platform for Synergistic Anti‐Inflammatory and Microbiota Modulation Therapy of Inflammatory Bowel Disease

ABSTRACT Intravenous antibody administration and oral delivery of probiotic‐derived outer membrane vesicle (OMVs) for the management of inflammatory bowel disease are limited by multiple physiological barriers, including gastric acid, intestinal mucus, and the epithelial cell barrier. Here, we report a probiotic‐derived oral dual‐triggered platform consisting of an outer pH‐responsive hydrogel matrix and inner acoustic‐triggered microbubble cores, which sequentially overcome the physiological barriers of the gastrointestinal tract. In the acidic gastric environment, the hydrogel matrix forms stable cavities that effectively protect the internal microbubbles from acid while transmitting the ultrasound energy to the inner cores. Derived from Escherichia coli Nissle 1917 OMVs, the inner acoustic‐triggered microbubbles inherited approximately 65.2% of proteins, with an anti‐TNF‐α agent decorated on their surface. We demonstrate that the oral dual‐triggered platform maintains excellent acoustic responsiveness throughout the gastrointestinal tract. The acoustic‐triggered microbubble‐to‐nanovesicles transformation carries both OMVs and antibody components, achieving synergistic therapeutic effects by blocking proinflammatory cytokines and modulating the gut microbiota. Our findings provide new insights into the rational design of bioinspired materials‐driven synergistic anti‐inflammatory and microbiota‐modulating therapy of inflammatory bowel disease.