A living Nanosilver-Probiotic therapeutic orchestrate Wnt-driven barrier repair and microbiota normalization in TNBS-induced murine colitis model

Inflammatory bowel disease (IBD) results from dysregulated interactions among gut microbiota, mucosal immunity, and host genetics factors, ultimately leading to chronic inflammation and compromise of the epithelial barrier. Existing therapies remain inadequate for many patients, emphasizing the need for strategies that simultaneously target pathogens, maintain barrier integrity, and modulate host responses. Here, we engineer a living nanomaterial therapeutic by coupling the probiotic Bacillus licheniformis with in situ-grown 7-nm nanosilver to creat a probiotic-nanosilver composite and evaluated its efficacy in TNBS-induced murine colitis. In vivo, Nano-Ag-probiotic enhanced survival in a dose-dependent manner, attenuated weight loss and disease activity, and restored both colon length and histology architecture. Mechanistically, the treatment reinforced epithelial integrity by restoring physiological Wnt/β-catenin signaling, inhibiting GSK3β activation, and re-establishing tight-junction scaffolds including ZO-1, occludin, and claudins. These effects were accompanied by attenuation of pro-inflammatory cytokine signaling and downregulation of CCR2, indicating reduced recruitment of inflammatory monocytes. 16S rRNA sequence analysis revealed that Nano-Ag-probiotic treatment restored microbial diversity, improved Firmicutes/Proteobacteria ratio, reduced Bacteroides and enriched SCFA-associated Dorea in TNBS-induced colitis. Collectively, these data demonstrate that the nanosilver composite rebalances the microbiota-barrier-immunity axis in experimental colitis and represents a translationally promising platform for managing infection-exacerbated intestinal inflammation.