Engineered commensal microbes for diet-mediated colorectal-cancer chemoprevention

Nat Biomed Eng. 2018 Jan;2(1):27-37. doi: 10.1038/s41551-017-0181-y. Epub 2018 Jan 10.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anticarcinogenic Agents / administration & dosage*
  • Anticarcinogenic Agents / metabolism
  • Cell Adhesion
  • Cell Line, Tumor
  • Chemoprevention / methods*
  • Colorectal Neoplasms / microbiology*
  • Colorectal Neoplasms / prevention & control*
  • Disease Models, Animal
  • Escherichia coli / enzymology*
  • Gastrointestinal Microbiome*
  • Glucosinolates / administration & dosage*
  • Glucosinolates / metabolism
  • Glycoside Hydrolases / metabolism
  • Heparan Sulfate Proteoglycans / metabolism
  • Isothiocyanates / metabolism
  • Male
  • Mice, Inbred BALB C

Substances

  • Anticarcinogenic Agents
  • Glucosinolates
  • Heparan Sulfate Proteoglycans
  • Isothiocyanates
  • Glycoside Hydrolases
  • thioglucosidase
  • sulphoraphene