Fig. 3

Effects of metabolites of probiotics on intestinal epithelial barrier. Indole 3-propionic acid can bind to PXR and up-regulate the expression of tight junction protein. The indole-3-lactic acid activates AhRs of the gut epithelium and promotes the expression of IL-22. The soluble proteins P40 and p75 isolated from LGG can activate EGFR and then up-regulate the expression of an APRIL in the epithelium, thus stimulating the secretion of lgA by B cells. Besides, P40 and p75 can activate EGFR–PIK3–Akt signaling pathway to maintain gut homeostasis. Moreover, these two proteins also prevent tight junctional disruption by protein kinase C (PKC)-dependent mechanisms. Butyrate is able to bind to the GPCR including GPR41, GPR109A, and GPR43 and induce the production of IL-18 in the colonic epithelium. Furthermore, butyrate also motivates the O₂ consumption of the gut epithelium to maintain HIF stability and increase the expression of barrier-protective HIF target genes. In addition, bacteriocins produced by probiotics act as colonizing peptides to encourage producers to gain a competitive advantage over other strains and to occupy established niches in the intestines. Alternatively, bacteriocins can act as a killing peptide, directly inhibiting the adhesion of pathogens to the mucus layer and protecting the first barrier of the intestinal tract. HIF hypoxia-inducible factor, GPR109A G-protein-coupled receptors 109A, AhRs aryl hydrogen receptors, P75 and P40 cell wall-associated hydrolase, EGFR epidermal growth factor receptor, PI3K phosphatidylinositol-3-kinase, PKC protein kinase C, PXR pregnane X receptor, APRIL a proliferation-inducing ligand, PKC protein kinase C