Engineered Probiotic-Silver Nanointerfaces Enable Multimodal Repair of Inflamed Colon via Wnt and Chemokine Recalibration

The pathogenesis of inflammatory bowel disease involves interconnected failures in epithelial integrity, immune cell migration, and inflammatory homeostasis in the system, making multifunctional therapeutic approaches a promising option. In this study, we developed a Bacillus licheniformis-templated nano-silver (Nano-Ag) composite within a tannic acid-iron (TA-Fe) metal-phenolic network and evaluated its therapeutic effects in TNBS-induced colitis. The composite exhibited favorable physicochemical properties, including a stable surface architecture and uniform nanosilver deposition, supporting its potential application as a biohybrid nanotherapeutic platform. In vivo treatment produced a dose-responsive protective effect, with the 1 mg formulation showing the most consistent response. This treatment regimen improved survival, reduced morbidity, alleviated diarrhea and fecal bleeding, lowered disease activity, preserved colon length, and significantly restored colonic histoarchitecture. Further histological examination revealed reduced inflammatory infiltration and improved hepatic morphology, indicating protective effects beyond the intestine. At the molecular level, therapeutic efficacy was associated with LEF-1 suppression, axin restoration, CXCR2 and CCR7 attenuation, and CCR5 recovery, consistent with coordinated normalization of Wnt-associated epithelial signaling and chemokine-guided immune trafficking. Serum profiling further revealed broad modulation of dysregulated chemokine networks and partial correction of biochemical disturbances associated with gut-liver and gut-kidney axis dysfunction. Collectively, these findings indicate that the engineered biohybrid nano-Ag platform does not act through a single anti-inflammatory mechanism, but rather through integrated remodeling of epithelial repair, inflammatory signaling, and systemic metabolic stress. Our study identifies TA-Fe-stabilized probiotic nano-Ag therapy as a promising multifunctional strategy for experimental colitis and provides a mechanistic framework for developing next-generation nanomedicines for inflammatory bowel disease.