Baicalin nanoengineered probiotics synergistically suppress IL-6/STAT3 signaling and remodel gut microbiota for Crohn’s disease therapy

Crohn’s disease (CD) is chronic inflammatory bowel disorder characterized by transmural inflammation, intestinal barrier disruption, and gut microbiota dysbiosis. Although probiotics show therapeutic potential for CD through modulating the intestinal flora, conventional oral formulations are constrained by low survival rates in the gastrointestinal tract and limited efficacy. Inspired by the metal-coordinating property and anti-inflammatory effect of baicalin (BA), the nanoengineered probiotics Fe-BT@EcN are developed through synergy with tannic acid and ferric ions, demonstrating enhanced resistance to adverse gastric environment as well as improved intestinal adhesion and colonization. Notably, as confirmed by network pharmacology and molecular docking studies, BA targets dual therapeutic pathways in CD intervention to elevate antioxidant and anti-inflammatory activities through regulation of reactive oxygen species (ROS) levels and inhibition of the IL-6/STAT3 signaling pathway. In a murine 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced CD model, Fe-BT@EcN exhibited synergistic therapeutic efficacy by alleviating colonic inflammation, restoring epithelial barrier function, and reestablishing microbial homeostasis. This study provides a feasible strategy to develop multifunctional oral microecologics for CD treatment through leveraging different probiotics and natural bioactive small molecules.