Fcgbp in colon mucus is terminally-sialylated and limits colonic inflammation 4285

Abstract Description Gut barrier mechanisms that limit invasion of the intestinal epithelium by commensals help to reduce susceptibility to inflammatory bowel disease (IBD). Glycosylation and terminal sialylation of intestinal mucins help to maintain barrier integrity, but the role of other mucus proteins in the protective glycosylation of the colon mucus barrier is unclear. The Fc fragment of IgG binding protein (FCGBP) is a major constituent of intestinal mucus and reduced FCGBP has been detected in the structurally weakened mucus of ulcerative colitis (UC) patients. However, the exact roles of Fcgbp in intestinal homeostasis remains unknown. Here, we show that in mice in which Fcgbp is either reduced (Fcgbp+/-) or completely ablated (Fcgbp-/-), there is decreased abundance of terminal α-2,6 sialylation in the colon mucus layer. Interestingly, this results in increased bacterial proximity to the colonic epithelium, more compensatory IgA sequestration of commensal bacteria, and expansion of mucus-dwelling pathobiont Mucispirillum Shaedleri. Utilizing a mouse model of UC, we found that relative to wild type littermates, Fcgbp+/- mice show rapid localization of bacteria at the epithelial border, and severe colitis in both acute and chronic stages of disease. Collectively, our findings indicate that Fcgbp enhances gut barrier defense through protective mucus α-2,6 sialylation, thereby limiting bacterial penetration of the colon epithelium and susceptibility to commensal-driven colonic inflammation. Funding Sources RO1 AI162736 Topic Categories Mucosal and Regional Immunology (MUC)