Metal-Phenolic Network Directed Coating of Single Probiotic Cell Followed by Photoinitiated Thiol-Ene Click Fortification to Enhance Oral Therapy

Probiotics-based oral therapy has become a promising way to prevent and treat various diseases, while the application of probiotics is primarily restricted by loss of viability due to adverse conditions in the gastrointestinal (GI) tract during oral delivery. Layer-by-layer (LbL) single-cell encapsulation approaches are widely employed to improve the bioavailability of probiotics. However, they are generally time- and labor-intensive owing to multistep operation. Herein, a simple yet efficient LbL technique is developed to coat a model probiotic named Escherichia coli Nissle 1917 (EcN) through polyphenol-Ca2+ network directed allyl-modified gelatin (GelAGE) adsorption followed by cross-linking of GelAGE via photoinitiated thiol-ene click reaction to protect EcN from harsh microenvironments of GI tract. LbL single-cell encapsulation can be performed within 1 h through simple operation. It is revealed that coated EcN exhibits significantly improved viability against acidic gastric fluid and bile salts, and enhanced colonization in the intestinal tract without loss of proliferation capabilities. Furthermore, oral therapy of coated EcN remarkably relieves the pathological symptoms associated with colitis in mice including down-regulating inflammation, repairing epithelial barriers, scavenging reactive oxygen species (ROS), and restoring the homeostasis of gut microbiota. This simplified LbL coating strategy has great potential for various probiotics-mediated biomedical and nutraceutical applications. To achieve beneficial effects on the host, oral delivery of probiotics must overcome challenges such as gastric acid and bile salt. Conventional layer-by-layer single-cell encapsulation approaches need tedious multilayer coatings to ensure satisfactory protection. This work has developed a novel metal-phenolic network-directed gelatin fortification coating method, which affords remarkable protection for probiotics and greatly simplifies the operation.image

Automated summary

A simplified layer-by-layer encapsulation technique has been developed to protect probiotics from adverse conditions in the gastrointestinal tract. The coated probiotics show improved viability and colonization in the intestinal tract, and oral therapy with the coated probiotics alleviates colitis symptoms in mice. This study has significant implications for probiotics-mediated biomedical and nutraceutical applications.