Abstract
The colorectal mucosal epithelium is composed of rapidly proliferating crypt cells derived by clonal expansion from stem cells. The aging human colorectal mucosa develops aberrant patterns of DNA methylation that may contribute to its increasing vulnerability to cancer. Various types of evidence suggest that age-dependent loss of global methylation, together with hypermethylation of CpG islands associated with cancer-related genes, may be influenced by nutritional and metabolic factors. Folates are essential for the maintenance of normal DNA methylation, and folate metabolism is known to modify epigenetic mechanisms under experimental conditions. Human intervention trials and cross-sectional studies suggest a role for folates and other nutritional and metabolic factors as determinants of colorectal mucosal DNA methylation. Future studies should focus on the possibility that folic acid fortification may exert unforeseen effects on the human gastrointestinal epigenome. Naturally occurring DNA methyltransferase inhibitors in plant foods may be useful for the manipulation of epigenetic profiles in health and disease.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.