Carnobacterium maltaromaticum boosts intestinal vitamin D production to suppress colorectal cancer in female mice

Qing Li(Chinese University of Hong Kong), Hung Chan(Chinese University of Hong Kong), Weixin Liu(Chinese University of Hong Kong), Changan Liu(Chinese University of Hong Kong), Yunfei Zhou(Chinese University of Hong Kong), Dan Huang(Chinese University of Hong Kong), Xueliang Wang(The First Affiliated Hospital, Sun Yat-sen University), Xiaoxing Li(The First Affiliated Hospital, Sun Yat-sen University), Chuan Xie(Chinese University of Hong Kong), Wing Ying-Zhi Liu(Chinese University of Hong Kong), Xiansong Wang(Chinese University of Hong Kong), Siu Kin Ng(Chinese University of Hong Kong), Hongyan Gou(Chinese University of Hong Kong), Liuyang Zhao(Chinese University of Hong Kong), Winnie Fong(Chinese University of Hong Kong), Lanping Jiang(Chinese University of Hong Kong), Yufeng Lin(Chinese University of Hong Kong), Guijun Zhao(Inner Mongolia People's Hospital), Feihu Bai(Hainan Medical University), Xiaodong Liu(Chinese University of Hong Kong), Huarong Chen(Chinese University of Hong Kong), Lin Zhang(Chinese University of Hong Kong), Sunny H. Wong(Nanyang Technological University), Matthew T.V. Chan(Chinese University of Hong Kong), William Ka Kei Wu(Chinese University of Hong Kong), Jun Yu(Chinese University of Hong Kong)
Cancer Cell
July 20, 2023
10.1016/j.ccell.2023.06.011
Cited by 108Open Access
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Abstract

Carnobacterium maltaromaticum was found to be specifically depleted in female patients with colorectal cancer (CRC). Administration of C. maltaromaticum reduces intestinal tumor formation in two murine CRC models in a female-specific manner. Estrogen increases the attachment and colonization of C. maltaromaticum via increasing the colonic expression of SLC3A2 that binds to DD-CPase of this bacterium. Metabolomic and transcriptomic profiling unveils the increased gut abundance of vitamin D-related metabolites and the mucosal activation of vitamin D receptor (VDR) signaling in C. maltaromaticum-gavaged mice in a gut microbiome- and VDR-dependent manner. In vitro fermentation system confirms the metabolic cross-feeding of C. maltaromaticum with Faecalibacterium prausnitzii to convert C. maltaromaticum-produced 7-dehydrocholesterol into vitamin D for activating the host VDR signaling. Overall, C. maltaromaticum colonizes the gut in an estrogen-dependent manner and acts along with other microbes to augment the intestinal vitamin D production to activate the host VDR for suppressing CRC.

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