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

Qing Li; Hung Chan; Wei-Xin Liu; Chang-An Liu; Yunfei Zhou; Dan Huang; Xueliang Wang; Xiaoxing Li; Chuan Xie; Wing Ying-Zhi Liu; Xian-Song Wang; Siu Kin Ng; Hongyan Gou; Liu-Yang Zhao; Winnie Fong; Lanping Jiang; Yufeng Lin; Guijun Zhao; Feihu Bai; Xiaodong Liu; Huarong Chen; Lin Zhang; Sunny Hei Wong; Matthew Tak Vai Chan; William Ka Kei Wu; Jun Yu

doi:10.1016/j.ccell.2023.06.011

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

Cancer Cell. 2023 Aug 14;41(8):1450-1465.e8. doi: 10.1016/j.ccell.2023.06.011. Epub 2023 Jul 20.

Authors

Qing Li¹, Hung Chan², Wei-Xin Liu³, Chang-An Liu³, Yunfei Zhou³, Dan Huang², Xueliang Wang⁴, Xiaoxing Li⁵, Chuan Xie², Wing Ying-Zhi Liu², Xian-Song Wang², Siu Kin Ng³, Hongyan Gou³, Liu-Yang Zhao³, Winnie Fong³, Lanping Jiang³, Yufeng Lin³, Guijun Zhao⁶, Feihu Bai⁷, Xiaodong Liu², Huarong Chen¹, Lin Zhang⁸, Sunny Hei Wong⁹, Matthew Tak Vai Chan¹⁰, William Ka Kei Wu¹¹, Jun Yu¹²

Affiliations

¹ State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Anaesthesia and Intensive Care and Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
² Department of Anaesthesia and Intensive Care and Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
³ State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.
⁴ State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
⁵ Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
⁶ Department of Endoscopy Center, Inner Mongolia Key Laboratory of Endoscopic Digestive Disease, Inner Mongolia people's Hospital, Hohhot, China.
⁷ Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China.
⁸ Department of Anaesthesia and Intensive Care and Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.
⁹ State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
¹⁰ Department of Anaesthesia and Intensive Care and Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China. Electronic address: mtvchan@cuhk.edu.hk.
¹¹ State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Anaesthesia and Intensive Care and Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China. Electronic address: wukakei@cuhk.edu.hk.
¹² State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. Electronic address: junyu@cuhk.edu.hk.

PMID: 37478851
DOI: 10.1016/j.ccell.2023.06.011

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.

Keywords: 7-DHC; VDR; colon cancer; estrogen; probiotics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carnobacterium / metabolism
Colorectal Neoplasms*
Estrogens / metabolism
Female
Mice
Receptors, Calcitriol / genetics
Receptors, Calcitriol / metabolism
Vitamin D* / metabolism

Substances

Vitamin D
Estrogens
Receptors, Calcitriol

Supplementary concepts

Carnobacterium maltaromaticum