Engineered commensal microbes for diet-mediated colorectal-cancer chemoprevention.
Chun Loong Ho, Hui Qing Tan, Koon Jiew Chua, Aram Kang, Kiat Hon Lim, Khoon Lin Ling, Wen Shan Yew, Yung Seng Lee, Jean Paul Thiery, Matthew Wook Chang
Author Information
Chun Loong Ho: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Hui Qing Tan: Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore.
Koon Jiew Chua: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Aram Kang: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Kiat Hon Lim: Department of Pathology, Singapore General Hospital, Singapore, Singapore.
Khoon Lin Ling: Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore.
Wen Shan Yew: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Yung Seng Lee: NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, Singapore, Singapore. ORCID
Jean Paul Thiery: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Matthew Wook Chang: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. matthew_chang@nuhs.edu.sg. ORCID
Chemoprevention-the use of medication to prevent cancer-can be augmented by the consumption of produce enriched with natural metabolites. However, chemopreventive metabolites are typically inactive and have low bioavailability and poor host absorption. Here, we show that engineered commensal microbes can prevent carcinogenesis and promote the regression of colorectal cancer through a cruciferous vegetable diet. The engineered commensal Escherichia coli bound specifically to the heparan sulphate proteoglycan on colorectal cancer cells and secreted the enzyme myrosinase to transform host-ingested glucosinolates-natural components of cruciferous vegetables-to sulphoraphane, an organic small molecule with known anticancer activity. The engineered microbes coupled with glucosinolates resulted in >95% proliferation inhibition of murine, human and colorectal adenocarcinoma cell lines in vitro. We also show that murine models of colorectal carcinoma fed with the engineered microbes and the cruciferous vegetable diet displayed significant tumour regression and reduced tumour occurrence.
