Ketogenic diet stimulates tumor cGAS-Sting pathway and attenuates systemic inflammation via Flavonifractor plautii derived uridine
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. Ketogenic diets are reported to regulate cancer progression and therapy response. Here, the authors show that a ketogenic diet boosts microbial uridine, activates tumor immune signaling, slows tumor growth, and dampens brain inflammation in mouse cancer models.
Authors
- Xiaoxia Jiang (ORCID: https://orcid.org/0000-0003-1401-9653)
- Lingyu Zhang (ORCID: https://orcid.org/0000-0003-1275-1824)
- Shengtao Zhu (ORCID: https://orcid.org/0000-0002-2795-8943)
- Ziwen Wang (ORCID: https://orcid.org/0000-0001-6757-4752)
- Hanping Shi (ORCID: https://orcid.org/0000-0003-4514-8693)
- Zhenhua Xu (ORCID: https://orcid.org/0009-0005-1894-7555)
- Zengqiang Yuan (ORCID: https://orcid.org/0000-0001-5739-2867)
- Yan Wang (ORCID: https://orcid.org/0000-0002-3711-5202)
- Chuang Xu (ORCID: https://orcid.org/0000-0002-0377-1439)
- Chenan Liu
- Huaqiang Ruan
- Jianing Wang
- Xiangrui Li (ORCID: https://orcid.org/0009-0002-5252-3172)
- Meng Tang
- Zhaoting Bu
- Shengjie Wang
- Xin Zheng
- Yue Chen
- Hong Zhao
- Zhenwen Chen
- Yulong Chen
- Heyang Zhang
- Tong Liu
- Hui Hu
- Xiaoyue Liu
- Jinyu Shi
- Changyi Luo
- Guotian Ruan
- Bomin Guo
- Qiaozhen Qin
- Hailun Xie
- Li Deng
- Shiqi Lin
- Xiaotong Li
- Chong Li
Institutions
- Capital Medical University (CN)
- Anhui Medical University (CN)
- First Affiliated Hospital of Wenzhou Medical University (CN)
- Chinese PLA General Hospital (CN)
- First Affiliated Hospital of Chinese PLA General Hospital (CN)
- Beijing Friendship Hospital (CN)
- Beijing Shijitan Hospital (CN)
- Chongqing Dazu District People's Hospital (CN)
- Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences (CN)
- Chongqing Medical University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-11-02
- DOI
- https://doi.org/10.1038/s41467-026-78868-0
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- École Nationale d’Ingénieurs de Saint-Etienne