Antioxidant and immunomodulator nanoengineered probiotics for synergistic therapy of inflammatory bowel disease

Inflammatory bowel disease (IBD) is marked by elevated reactive oxygen species (ROS) and pro-inflammatory cytokines, as well as disrupted gut microbiota. Utilizing probiotics presents a compelling strategy to relieve IBD, while enhancing their bioavailability and therapeutic efficacy within the complex gastrointestinal environment remains a challenge. Herein, probiotic Escherichia coli Nissle 1917 (EcN) was nanoengineered with a natural antioxidant, bilirubin (BR), and bio-orthogonally conjugated with an immunomodulator, hyaluronic acid (HA), to produce EcN-BR/HA for the synergistic treatment of IBD. The HA nanocoating layer protected probiotics from the harsh gastric attacks, while swelled to activate probiotics in the neutral condition of intestinal tract. Besides eliminating ROS and polarizing macrophage into alternatively activated type in vitro, EcN-BR/HA could effectively alleviate IBD upon oral administration by scavenging ROS, reducing the proinflammatory cytokines, reinforcing the intestinal barrier, and balancing the gut microbiota homeostasis in a mouse model. This work provided an innovative strategy to design robust and multifunctional probiotics for enhanced therapeutic potential against IBD.