Bacteroides cellulosilyticus-directed glycans relieve colitis

Bacteroides cellulosilyticus correlates with inflammatory bowel disease (IBD). Targeting an increase in abundance of B. cellulosilyticus is a feasible approach to treating IBD. Although B. cellulosilyticus is responsive to dietary components, untargeted manipulation can lead to an increase in harmful bacteria in the microbiota. Despite breakthroughs in methods for regulating specific microbes, the protocols are expensive, time-consuming, and difficult to follow. Glycans based on microbial-carbohydrate-active enzymes (CAZymes) that target a specific microbiota would provide a potential solution. We propose a method based on microbiota-specific CAZymes to design polysaccharides that target specific gut microbes and have the potential to alleviate diseases. The designed polysaccharides (Arabinogalactan, AG) enrich the abundance of B. cellulosilyticus in single-strain co-cultures, fermentation in vitro, and mouse models in vivo. Supplementation with AG created using our method relieved mice from colitis and clinical symptoms. Our glycan design pipeline is a promising pathway to improve IBD through the targeted enhancement of specific microbes.