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

Jiali Yang; Mengyun Peng; Shaochong Tan; Shengchan Ge; Li Xie; Tonghai Zhou; Wei Liu; Kaixiang Zhang; Zhenzhong Zhang; Junjie Liu; Jinjin Shi

doi:10.1021/acscentsci.3c00227

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

ACS Cent Sci. 2023 Jun 21;9(7):1327-1341. doi: 10.1021/acscentsci.3c00227. eCollection 2023 Jul 26.

Authors

Jiali Yang^{1

2}, Mengyun Peng^{1

2}, Shaochong Tan^{1

2}, Shengchan Ge^{1

2}, Li Xie^{1

2}, Tonghai Zhou^{1

2}, Wei Liu^{1

2}, Kaixiang Zhang^{1

2

3}, Zhenzhong Zhang^{1

2

3}, Junjie Liu^{1

2

3}, Jinjin Shi^{1

2

3

4}

Affiliations

¹ School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, P. R. China.
² Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou 450001, P. R. China.
³ Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001, P. R. China.
⁴ State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou, 450001, P. R. China.

Abstract

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.