NIR light-responsive bacteria with live bio-glue coatings for precise colonization in the gut

Recombinant bacterial colonization plays an indispensable role in disease prevention, alleviation, and treatment. Successful application mainly depends on whether bacteria can efficiently spatiotemporally colonize the host gut. However, a primary limitation of existing methods is the lack of precise spatiotemporal regulation, resulting in uncontrolled methods that are less effective. Herein, we design upconversion microgels (UCMs) to convert near-infrared light (NIR) into blue light to activate recombinant light-responsive bacteria (Lresb) in vivo, where autocrine "functional cellular glues" made of adhesive proteins assist Lresb inefficiently colonizing the gut. The programmable engineering platform is further developed for the controlled and effective colonization of Escherichia coli Nissle 1917 (EcN) in the gut. The colonizing bacteria effectively alleviate DSS-induced colitis in mice. We anticipate that this approach could facilitate the clinical application of engineered microbial therapeutics to accurately and effectively regulate host health.