Commensal bacteria, redox stress, and colorectal cancer: Mechanisms and models

Mark M. Huycke, H. Rex Gaskin

Research output: Contribution to journalShort surveypeer-review

Abstract

The potential role for commensal bacteria in colorectal carcinogenesis is explored in this review. Most colorectal cancers (CRCs) occur sporadically and arise from the gradual accumulation of mutations in genes regulating cell growth and DNA repair. Genetic mutations followed by clonal selection result in the transformation of normal cells into malignant derivatives. Numerous toxicological effects of colonic bacteria have been reported. However, those recognized as damaging epithelial cell DNA are most easily reconciled with the currently understood genetic basis for sporadic CRC. Thus, we focus on mechanisms by which particular commensal bacteria may convert dietary procarcinogens into DNA damaging agents (e.g., ethanol and heterocyclic amines) or directly generate carcinogens (e.g., fecapentaenes). Although these and other metabolic activities have yet to be linked directly to sporadic CRC, several lines of investigation are reviewed to highlight difficulties and progress in the area. Particular focus is given to commensal bacteria that alter the epithelial redox environment, such as production of oxygen radicals by Enterococcus faecalis or production of hydrogen sulfide by sulfate-reducing bacteria (SRB). Superoxide-producing E. faecalis has conclusively been shown to cause colonic epithelial cell DNA damage. Though SRB-derived hydrogen sulfide (H2S) has not been reported thus far to induce DNA damage or function as a carcinogen, recent data demonstrate that this reductant activates molecular pathways implicated in CRC. These observations combined with evidence that SRB carriage may be genetically encoded evoke a working model that incorporates multifactorial gene-environment interactions that appear to underlie the development of sporadic CRC.

Original languageEnglish (US)
Pages (from-to)586-597
Number of pages12
JournalExperimental Biology and Medicine
Volume229
Issue number7
DOIs
StatePublished - Jul 2004

Keywords

  • Chromosomal instability
  • Colonic microbiota
  • Colorectal cancer
  • Enterococcus faecalis
  • Redox stress
  • Sulfate-reducing bacteria

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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