Targeting IBD via molecular dissection of gut bacterial mucus degradation

Inflammatory Bowel Disease (IBD), which includes conditions like Crohn’s disease and ulcerative colitis, affects millions of people and causes painful gut inflammation. Recent research suggests that abundant gut bacteria from the group Bacteroides play a complicated role in IBD. These bacteria help us use dietary carbohydrates but can also damage the protective mucus lining of the large intestine by consuming protective sugar molecules in mucus, called O-glycans, triggering inflammation and exacerbating disease. When Bacteroides bind and uptake O-glycans, the cells become activated to degrade the mucus layer. Our project aims to uncover exactly how Bacteroides recognize and uptake O-glycans, the first gatekeeping step that leads to mucus breakdown and subsequent inflammation. We are using newly developed synthetic chemistry techniques to create pure versions of O-glycans and will study how different Bacteroides species react to them. We’ll also use advanced imaging to reveal how special bacterial surface proteins recognize and uptake these sugars. Understanding these earliest steps will help us design targeted treatments that stop harmful mucus breakdown—without killing off helpful bacteria—preserving gut health. These cutting-edge discoveries could lead to new therapies for IBD and related diseases, offering hope to patients and families for gentler, more precise treatments.