Fig. 2.

Immunomodulatory effect of protein/amino acid metabolites on the colon. Tryptophan promotes the expression of the tight junction protein to achieve the intestinal barrier function. Aryl hydrocarbon receptor (AHR), which is a crucial ligand-dependent transcription regulator in the cytoplasm, can bind to tryptophan and its downstream metabolites. The resulting complex is transported to the nucleus, where the AHR is activated. This regulates the proliferation and differentiation of intestinal inflammatory cells and the transcription and expression of inflammatory-related factors (such as interleukin-22, IL-22). Short-chained fatty acids regulate protective immunity and tissue inflammation by controlling intestinal epithelial cells (IEC), promoting the development of regulatory T cells (Treg), enhancing the secretion of mucus by goblet cells, and promoting IL-18 in T cells. Short-chain fatty acid receptor 2 and 3 (FFA2 and FFA3) are essential regulators of intestinal inflammation and epithelial barrier function. Short-chain fatty acid receptor 2 regulates the Treg development. Short-chain fatty acid receptor 2 on dendritic cells can also promote the production of intestinal IgA. Different from FFA2, FFA3 (which is expressed in the intestinal nonimmune cell population) enhances the expression of transforming growth factor-α, IL-6, and other cytokines and chemokines mainly through mitogen-activated protein (MAPK)/extracellular signal-regulated kinases pathway; short-chained fatty acids can promote IEC to produce antimicrobial peptides (AMP) through FFA2. Some amino acids significantly stimulate the expression of β-defensin in epithelial cells by blocking nuclear factor kappa-B (NF-κB) and MAPK inflammatory signaling pathways and activating the mammalian target of rapamycin signaling pathway.