The intestinal epithelial barrier allows a large number of metabolites and immune signals to pass in both directions while blocking the pathways of pathogenic bacteria, toxic metabolites, and microbial byproducts. The outermost layer of the intestinal barrier is the mucus layer which is composed of mucin glycoprotein, AMPs, and sIgA, produced by goblet cells, Paneth cells, and plasma cells, respectively, and excludes the microbiome from the epithelial surface. Adjacent cells are linked together by the tight junction protein families that can determine the permeability and prevent mechanical disruption of the epithelial sheet. The intestinal immune system is established and mature with the participation of the gut microbiota. Once bound to luminal antigens, DC pattern recognition receptors express costimulatory molecules and cellular factors involved in regulating Th1, Th2, Th17, and Treg cells differentiated from naive CD4+ T cells, maintaining Treg/Th17 balance and forming immune homeostasis. The intestinal microbiome promotes the differentiation of IgA-secreting plasma cells by activating APRIL (a proliferation-inducing ligand) receptor and B cell-activating factor in DC.