Ketogenic diet exacerbates DSS-induced colitis through a β-hydroxybutyrate-Thomasclavelia spiroformis-γδ17 T cell axis in mice

mice confirmed their pathogenicity. Ketogenesis or IL-17A blockades abolish KD-exacerbated colitis, whereas β-HB supplementation or ketogenesis activation recapitulated disease exacerbation. Clinically, T. spiroformis abundance correlates with fecal β-HB and serum IL-17A in ulcerative colitis (UC) patients, but not Crohn's disease, supporting a UC-specific β-HB-T. spiroformis-γδ17 T cell axis. Thus, we identify a diet-induced immunometabolic circuit linking ketogenesis to colitis, highlighting ketone metabolism and IL-17A signaling as potential therapeutic targets.

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Journal
Nature Communications
Published
2026-04-23
DOI
https://doi.org/10.1038/s41467-026-72044-0
Primary Topic
Diet and metabolism studies
Type
article
Field-Weighted Citation Impact
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article

Ketogenic diet exacerbates DSS-induced colitis through a β-hydroxybutyrate-Thomasclavelia spiroformis-γδ17 T cell axis in mice

Cen Xie, Lei Chen, Frank J. Gonzalez, Xianchun Zhong et al.
Nature Communications
Diet and metabolism studies
article

Ketogenic diet exacerbates DSS-induced colitis through a β-hydroxybutyrate-Thomasclavelia spiroformis-γδ17 T cell axis in mice

Cen Xie, Lei Chen, Frank J. Gonzalez, Xianchun Zhong, Wei Xie, Li Chen, Weiwei Liu, Jingyi Xu, Shuai Li, Xuan Wu, Yueying Li, Weifeng Wang, Shan Wang, Xueting Yao, Lin Han, Yameng Liu
article en

Abstract

mice confirmed their pathogenicity. Ketogenesis or IL-17A blockades abolish KD-exacerbated colitis, whereas β-HB supplementation or ketogenesis activation recapitulated disease exacerbation. Clinically, T. spiroformis abundance correlates with fecal β-HB and serum IL-17A in ulcerative colitis (UC) patients, but not Crohn's disease, supporting a UC-specific β-HB-T. spiroformis-γδ17 T cell axis. Thus, we identify a diet-induced immunometabolic circuit linking ketogenesis to colitis, highlighting ketone metabolism and IL-17A signaling as potential therapeutic targets.

Nature Communications
National Institutes of Health (US), Nanjing University of Chinese Medicine (CN), Second Military Medical University (CN), Chinese Academy of Sciences (CN), Shanghai University of Traditional Chinese Medicine (CN), Longhua Hospital Shanghai University of Traditional Chinese Medicine (CN), Shanghai Institute of Materia Medica (CN), Shandong Provincial Hospital (CN), Ministry of Education (PT), Shanghai Tenth People's Hospital (CN), Eastern Hepatobiliary Surgery Hospital (CN), National Cancer Institute (US), Center for Cancer Research (US), Shandong Provincial QianFoShan Hospital (CN), Shandong First Medical University (CN), University of Chinese Academy of Sciences (CN)
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Diet and metabolism studies
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