Gut microbiota-derived deoxycholic acid shapes an immunosuppressive tumor microenvironment and promotes breast cancer progression

  • Cell Metab. 2026 May 12:S1550-4131(26)00149-X. doi: 10.1016/j.cmet.2026.04.011.
Lili Li  1 ,  Chenghui Yang  2 ,  Zhen Wang  3 ,  Bangyi Zhou  1 ,  Yixin Zhang  1 ,  Huiying Liu  1 ,  Shanshan Sun  4 ,  Mengyao Chen  1 ,  Xiaoxiao Hu  3 ,  Fang Jia  3 ,  Sangsang Zhu  3 ,  Miner Shao  1 ,  Jun Pan  3 ,  Leyi Zhang  3 ,  Xinyi Zhang  1 ,  Shuyan Yuan  1 ,  Jingxuan Zhu  1 ,  I Situ  1 ,  Jian Huang  5 ,  Fuming Qiu  6
Affiliations
  • 1. Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, P.R. China; Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, P.R. China.
  • 2. Department of Breast Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, P.R. China.
  • 3. Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, P.R. China; Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, P.R. China.
  • 4. Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, P.R. China.
  • 5. Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, P.R. China; Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, P.R. China. Electronic address: [email protected].
  • 6. Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, P.R. China; Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, P.R. China. Electronic address: [email protected].
PMID: 42127890 DOI: 10.1016/j.cmet.2026.04.011
Abstract

The gut microbiota is increasingly recognized as a contributor to breast Cancer progression. Here, we report that the gut bacterium Enteroclosterbolteae, a member of the Lachnospiraceae family, is progressively enriched during tumor development and is associated with increased levels of the microbiota-derived metabolite deoxycholic acid. Deoxycholic acid accumulates in tumors and activates the farnesoid X receptor in tumor cells, inducing interleukin-6 production through nuclear factor κB signaling. Interleukin-6 promotes the recruitment of granulocytic myeloid-derived suppressor cells and T helper 17 cells, establishing an immunosuppressive microenvironment. Inhibition or knockdown of the farnesoid X receptor, as well as blockade of interleukin-6 signaling, attenuates these effects. These findings identify a microbiota-metabolite-immune axis driving breast Cancer progression and uncover microbial metabolites as potential therapeutic targets.

Keywords
DCA; breast cancer; deoxycholic acid; gut microbiota; tumor immune-suppressive microenvironment.
Products