A mediterranean-mimicking diet harnesses gut microbiota–derived 3-IAA to rejuvenate T cell

Diet profoundly shapes the tumor microenvironment through metabolite modulation, yet the mechanisms linking diet, gut microbiota, and antitumor immunity remain unclear. Here, we demonstrate that a mediterranean-mimicking diet (MedDiet) suppresses tumor growth by orchestrating a microbiota–metabolite–immune axis. MedDiet selectively enriched Bacteroides thetaiotaomicron ( B. thetaiotaomicron ) in the gut, whose administration recapitulated tumor suppression. Both MedDiet and B. thetaiotaomicron elevated plasma levels of the tryptophan metabolite indole-3-acetic acid (3-IAA). Mechanistically, 3-IAA enhanced CD8 ⁺ T cell cytotoxicity and alleviated exhaustion by inhibiting the integrated stress response, sustaining antitumor immunity in vivo . Importantly, 3-IAA synergized with anti–PD-1 therapy to further restrain tumor progression. Finally, we developed a MedDiet Score to predict patient survival and response to immunotherapy. These findings reveal that dietary modulation of gut microbiota can reshape systemic metabolites to potentiate T cell–mediated antitumor responses. Our study identifies 3-IAA as a metabolite-based adjuvant for immune checkpoint therapy and highlights the translational potential of diet-driven immunomodulation in cancer treatment.