Intestinal amino acid metabolic response and its roles in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a group of chronic intestinal disorders driven by a complex interplay of environmental and genetic factors. Amino acids (AAs) play a pivotal role in modulating immune function and maintaining gut barrier integrity, which is strongly linked to the pathogenesis of IBD. The intestinal epithelium contains a variety of AA-sensing receptors and transporters that detect AA availability and dynamically reprogram host responses, thereby regulating intestinal physiology and immunological status. Additionally, the gut microbiota contributes significantly to the synthesis, supply, and metabolism of AAs within the gut lumen, and the changes in these AA-metabolizing bacterial strains markedly affect the occurrence of IBD. Both the host intestinal epithelium and the gut microbiota sense AAs at distinct spatial levels, which is essential for ensuring intestinal immune homeostasis. In this review, we highlight the potential roles of AAs and their metabolites in the pathogenesis of IBD. We provide an overview of recent findings on the effects of AA sensors and transporters on AA availability and their relevance to the pathogenesis of IBD. Finally, we summarize the roles of AA metabolites from the microbiota and their receptor signaling pathways in intestinal physiology and inflammation, which may inspire novel therapeutic opportunities for IBD.