Cancer progression is frequently accompanied by systemic inflammation and host-wide disturbances, including neuroinflammation-associated cognitive impairment, yet interventions that simultaneously target tumor growth and host dysfunction remain limited. Here we show that a ketogenic diet suppresses tumor growth while improving emotional and cognitive deficits in tumor-bearing mice. The diet elevates circulating and intratumoral uridine and enriches Flavonifractor plautii, a gut bacterium that contributes to host uridine availability. In tumor cells and patient-derived organoids, uridine cooperates with β-hydroxybutyrate to promote cytosolic DNA accumulation and activate cGAS–Sting signaling, consistent with enhanced antitumor immune activity. In parallel, ketogenic diet, uridine supplementation and F. plautii transplantation reduce systemic and hippocampal inflammatory readouts and improve neurobehavioral phenotypes. These findings identify a diet–microbiota–metabolite axis that links ketogenic metabolism to tumor immune signaling and reduced peripheral-to-brain inflammation in preclinical cancer models.

Full Paper - https://doi.org/10.1038/s41467-026-78868-0