Engineered Probiotics for Colitis Therapy by Improving Intestinal Colonization and Scavenging ROS

Probiotics hold significant promise for treating colitis, but their application remains challenging because of insufficient colonization and survival against colorectal oxidative stress. Herein, engineered probiotics were prepared to enhance probiotics' colonization and scavenge the overexpressed reaction oxygen species (ROS) at the site of colitis. First, primary amino groups on the Lactobacillus rhamnosus (LAB) surface were converted to free thiols by a simple one-step imidoester reaction. Then, we used thiol-initiated ring-opening cascade of dithiolanes to prepare a class of structurally dynamic microgels on the LAB surface (LAB-gel) by reacting alpha-lipoic acid (LA) and sodium thioctate (LANa). Finally, a lipid bilayer was coated on the surface of the LAB-gel to improve the stability of the microgel in gastric juice. Engineered probiotics survived an oxidative stress insult (100 μM H₂O₂) and were able to effectively colonize the colon. Furthermore, engineered probiotics could significantly uptake by macrophages and scavenge intracellular ROS. Engineered probiotics with enhanced colonization and ROS scavenging activity showed promising therapeutic effects on colitis.