Dietary Amino Acids and the Gut‐Microbiome‐Immune Axis: Physiological Metabolism and Therapeutic Prospects

Abstract Dietary amino acids (AAs) are not only absorbed and metabolized by enterocytes but also available to the microbiota in the gut in mammals. In addition to serving as the materials for protein synthesis, AAs can act as precursors for numerous metabolic end products in reactions involving the intestinal mucosa and microbiota. After penetrating the epithelial barrier, microbial metabolites can enter and accumulate in the host circulatory system, where they are sensed by immune cells and then elicit a wide range of biological functions via different receptors and mechanisms. Some intestinal bacteria can also synthesize certain AAs, implying that the exchange of AAs between hosts and microorganisms is bidirectional. Changes in AA composition and abundance can affect AA‐metabolizing bacterial communities and modulate macrophages and dendritic cells via toll‐like receptors (TLRs), autoinducer‐2 (AI‐2), and NOD‐like receptors (NLRs), and also regulate the gut‐microbiome‐immune axis via aryl hydrocarbon receptor (AhR), serotonin/5‐hydroxytryptamine (5‐HT), and other signaling pathways, all of which play critical roles in regulating the intestinal mucosal immunity and microbiota directly or indirectly, contributing to intestinal homeostasis. Therefore, the current findings of the effects of certain functional AAs on the gut‐microbiome‐immune axis are reviewed, illustrating signaling pathways of tryptophan (Trp), glutamine (Gln), methionine (Met), and branched‐chain AAs (BCAAs) in the intestinal barrier and regarding immunity via crosstalk with their receptors or ligands. These findings have shed light on the clinical applications of dietary AAs in improving gut microbiota and mucosal immunity, therefore benefiting the gut as well as local and systemic health.