Orally-Administrable Supramolecular Probiotic Capsules Enable Cooperative Colon-Targeted Inflammation Inhibition for Ameliorating Ulcerative Colitis.

Abstract

Ulcerative colitis (UC) is a prevalent gastrointestinal disease characterized by the chronical and refractory inflammation of colorectal mucosa and walls, which severely impairs overall well-being of individuals. Probiotics has shown tremendous promise for UC therapy due to its multifaceted mucosal barrier restoration and immunomodulation capabilities. Nevertheless, the successful administration of probiotics remains a clinical obstacle. Herein, we report a multifunctional supramolecular probiotic capsule based on clinically-tested biopolymers for UC therapy, which not only allow colon-targeted probiotic delivery via oral route but also enable concurrent delivery of hemostatic and anti-inflammatory drugs. Specifically, Clostridium butyricum (CB) was first engineered with protective norepinephrine (NE) coating and then encapsulated by self-assembled gelatin-based nanocomplexes modified with balsalazide and matrix metalloproteinase 2/9 (MMP2-/9)-responsive fibronectin peptides. The released balsalazide and fibronectin could induce rapid hemostasis and anti-inflammation actions to alleviate inflammation damage of the UC-affected colons in the short term, while CB could restore gut microbiota homeostasis to remodel intestinal immunocomposition and repair mucosal barrier for reducing UC risk in the long term. Overall, this study provides a promising option for UC treatment with good efficacy and minimal invasiveness. STATEMENT OF SIGNIFICANCE: This study reports a supramolecular probiotic capsule with nanointegrative hemostatic and anti-inflammatory capacities for ulcerative colitis (UC) therapy, which could be orally administrated and activated in the inflamed colorectal sites. The probiotic capsules enable immediate UC symptom relief while also accelerating mucosal repair and preventing UC relapse in the long-term, offering an approach for UC treatment in the clinic.