Gut microbiota-derived tryptophan metabolites: molecular mechanisms, nutritional strategies and implications for...

Tryptophan, an essential amino acid, has nutritional value. Beyond that, it is an important signaling molecule that connects the gut microbiota with host physiology. While host-mediated pathways are well-characterized, the microbiota-driven indole pathway has emerged as a major modulator of host homeostasis. Commensal bacteria metabolize unabsorbed tryptophan into indole-3-propionic acid (IPA), indole-3-lactic acid (ILA) and other bioactive indole derivatives. These bioactive indole derivatives can act as ligands for aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR). This review makes a summary of the main tryptophan metabolic pathways. It also elucidates the molecular mechanisms by which microbial metabolites derived from tryptophan restore the integrity of the intestinal barrier, maintain immune homeostasis, and modulate host metabolism. Building on this, we discuss nutritional strategies, such as dietary patterns and probiotic interventions, and their potential to modulate tryptophan metabolism. Using pigs as a translational model, we summarize the potential applications of these metabolites in alleviating weaning stress and improving growth performance. This review focuses on tryptophan metabolism and provides a theoretical basis for microbiome interventions and precision nutrition strategies in swine production.