Fig. 1: Diagrammatic representation of the interaction between the immune system, mucus layer, epithelial barrier, and microbiota in a homeostatic gut environment. A. Intact mucus layer, glycocalyx, and epithelial tight junctions restrict bacterial access to the epithelial barrier. Mucin glycans aid in colonization by acting as attachment points and as sources of nutrients. Mucin glycan sialylation protects the integrity of the mucus layer from bacterial proteolytic degradation. Fucosylation of mucin through FUT2 promotes positive growth. B.IL-4, IL-15, IL-22 secretion promotes mucus secretion, and IL-10 secretion prevents MUC2 misfolding in goblet cells. C . Secretory IgA secreted by IgA-secreting plasma cells regulates bacterial concentration in the mucosal layer. D. MAMPs trigger TLR-Myd88 signaling to induce antimicrobial peptides (i.e., RegIIIγ and α-defensins), which limit bacterial access to mucosal and epithelial layers. E. Mincle recognition of commensal bacteria in the gut inhibits IL-17 cytokine and Th17 cell responses through IL-6 and IL-23p19 cytokines. F. Anti-inflammatory responses maintain the homeostatic gut environment through Treg cell activity, Siglec activity, tolerogenic dendritic cells and macrophages, and galectin-1 activation.G. Commensal bacteria digest dietary (i.e., fiber) and host glycans through CAZymes to generate monosaccharides, disaccharides, and SCFAs, which are subsequently used as a nutrient and energy resource by the microbiota and host.