Calcium Tungstate Microgel Enhances the Delivery and Colonization of Probiotics during Colitis via Intestinal Ecological Niche Occupancy

[Image: see text] The effective delivery and colonization of probiotics are recommended for therapeutic interventions during colitis, the efficacy of which is hampered by abnormally colonized Enterobacteriaceae at pathological sites. To improve the delivery and colonization of probiotics, a calcium tungstate microgel (CTM)-based oral probiotic delivery system is proposed herein. CTM can selectively disrupt the ecological niche occupied by abnormally expanded Enterobacteriaceae during colitis to facilitate probiotic colonization. In addition, the calcium-binding protein, calprotectin, which is highly expressed in colitis, efficiently extracts calcium from CTM and releases tungsten to inhibit Enterobacteriaceae by displacing molybdenum in the molybdenum enzyme, without affecting the delivered probiotics. Moreover, CTM demonstrated resistance to the harsh environment of the gastrointestinal (GI) tract and to intestinal adhesion. The synergistic reduction of Enterobacteriaceae by 45 times and the increase in probiotic colonization by 25 times, therefore, result in a remarkable treatment for colitis, including restoration of colonic length, effective downregulation of the inflammatory response, restoration of the damaged mucosal barrier, and restoration of gut microbiome homeostasis.