Engineered Probiotics Secreting IL-18BP and Armed with Dual Single-Atom Catalysts for Synergistic Therapy in Ulcerative Colitis.

Ulcerative Colitis (UC) involves a complex pathological process characterized by excessive reactive oxygen species (ROS) production at lesion sites and gut microbiota dysregulation. Conventional therapies are often limited by their inability to concurrently address oxidative stress, immune dysregulation, and microbial imbalance. Herein, we developed an integrated bionanoplatform (DEI) by conjugating dual single-atom catalysts (DACs) with an engineered probiotic strain, Nissle 1917 (EcN). This EcN was genetically modified to stably express interleukin-18 binding protein (IL-18BP). The DACs effectively scavenge ROS in intestinal tissues via multienzyme mimetic activities, while IL-18BP neutralizes pro-inflammatory cytokines to modulate the inflammatory milieu. Orally administered, the engineered EcN delivers and retains the DACs within the intestine, significantly enhancing ROS neutralization. Concomitantly, the DACs augment colonization of the engineered EcN, thereby amplifying its therapeutic efficacy. In a dextran sulfate sodium-induced mouse colitis model, DEI effectively mitigated colitis symptoms, attenuated inflammation, and restored the abundance and diversity of the intestinal microbiota, promoting intestinal homeostasis. This multifunctional bionanoplatform thus offers a promising synergistic strategy for UC treatment by integrating ROS scavenging, immune modulation, and microbiota restoration.