Cell metabolism · 2026
Gut microbiota-derived deoxycholic acid shapes an immunosuppressive tumor microenvironment and promotes breast cancer progression.
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Li Lili, Yang Chenghui, Wang Zhen, Zhou Bangyi, Zhang Yixin, Liu Huiying, Sun Shanshan, Chen Mengyao, Hu Xiaoxiao, Jia Fang, Zhu Sangsang, Shao Miner, Pan Jun, Zhang Leyi, Zhang Xinyi, Yuan Shuyan, Zhu Jingxuan, Situ I, Huang Jian, Qiu Fuming
Аннотация
The gut microbiota is increasingly recognized as a contributor to breast cancer progression. Here, we report that the gut bacterium Enterocloster bolteae, 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.