Unlocking healthy aging through gut microbial tryptophan metabolism

Healthy aging has become an attractive focus of biomedical research worldwide. Tryptophan (Trp) metabolism pathways that yield kynurenine, indole derivatives, and 5-hydroxytryptophan during microbiota-host crosstalk regulate molecular processes critical to healthy aging. Here, we synthesize the most recent advances concerning the mechanisms by which microbial Trp metabolism maintains homeostasis from the perspectives of improving intestinal function, modulating immune signaling, restoring redox balance, and optimizing energy production. We further evaluate the latest evidence regarding how microbiota-derived Trp metabolites influence age-related disorders. Finally, we summarize the clinical applications of Trp metabolites and key metabolic enzymes to promote healthy aging. Our review provides comprehensive insights into the relationship between microbial Trp metabolism and human aging, and it opens up novel opportunities for prevention, diagnosis, and therapy of disease.