Modified Prebiotic-Based "Shield" Armed Probiotics with Enhanced Resistance of Gastrointestinal Stresses and Prolonged Intestinal Retention for Synergistic Alleviation of Colitis.

Abstract

Oral administration of probiotics is a promising method to alleviate inflammatory bowel diseases (IBDs). However, gastrointestinal environmental sensitivity and inferior intestinal colonization of probiotics hinder the alleviation effect. Here, we developed a simple yet effective modified prebiotic-based "shield" (Fe-TA@mGN) composed of an Fe3+-tannic acid cross-linking network and carboxymethylated β-glucan for arming Escherichia coli Nissle 1917 (EcN@Fe-TA@mGN). The Fe-TA@mGN "shield" not only acted as a dynamic barrier to enhance the gastrointestinal stress resistance ability of EcN but also aided the intestinal colonization of EcN as well as synergized with EcN for the alleviation of dextran sulfate sodium (DSS) induced colitis. More specifically, with the protection of the Fe-TA@mGN "shield", the survival rate of armed EcN could be up to ∼1720 times higher than that of bare EcN after exposure to simulated gastric fluid. Excitingly, the intestinal retention rate of EcN@Fe-TA@mGN was as high as 47.54 ± 6.06% at 16 h post-administration, while almost all bare EcNs were excreted out at 8 h post-administration. With all of the aforementioned attributes, EcN@Fe-TA@mGN efficiently alleviated colitis, verified by the repair of the intestinal barrier and the attenuation of inflammation. Moreover, for EcN@Fe-TA@mGN, mGN synergized with EcN to positively modulate gut microbiota and promote the production of short-chain fatty acids (SCFAs, especially for butyric acid, a primary source for maintaining intestinal health), both of which would further advance the alleviation of colitis. We envision that the strategy developed here will inspire the exploitation of various prebiotics to arm probiotics for the effective alleviation of IBD.