The gut microbiota-tryptophan metabolism-immune axis in inflammatory bowel disease: Mechanisms and therapeutic prospects

Abstract

ABSTRACT The gut microbiota–tryptophan (TRP) metabolism–immune axis is one of the core pathogenic mechanisms in inflammatory bowel disease (IBD). Physiologically, gut microbes convert dietary TRP into bioactive metabolites that regulate intestinal immune balance and barrier function via AHR. In IBD, this axis enters a vicious cycle of dysbiosis, metabolic disruption, and immune imbalance – characterized by reduced beneficial bacteria, excessive 5‑HT production, and kynurenine pathway overactivation – which drives T‑cell dysregulation, aberrant macrophage polarization, and compromised barrier integrity. Therapeutic strategies are shifting from single‑target to integrated approaches, combining probiotics, engineered bacteria, AHR agonists, IDO1 inhibitors, immunomodulators, and ROS‑responsive nanomedicines. By achieving multi‑node synergistic remodeling, this review provides a theoretical foundation for systemic strategies that coordinate microbial regulation, metabolic intervention, and immune targeting, thereby offering new avenues for the effective treatment of IBD.