Previous studies have found that alterations in colon-associated microbes can raise the risk of colorectal cancer (CRC) in humans.
Researchers attempted to uncover genetic mechanisms by which alterations in colon-associated microbes might promote CRC. Experiments in which fecal microbes were transferred from patients with CRC or from healthy controls to germ-free mice exposed to the carcinogen azoxymethane revealed that after 7–14 weeks of transfer, mice that received fecal microbes from CRC patients exhibited greater numbers of aberrant crypts in colonic tissues, as well as increased epithelial cell division, increased inflammation, and greater epigenetic changes in the colonic mucosa, compared with mice that received fecal microbes from healthy controls.
Next, the authors computed a cumulative methyl index (CMI)—a measure of DNA methylation changes in gene promoters—in blood samples from a cohort of participants with normal colonoscopies as well as patients with CRC.
In a pilot study of 266 people, blood DNA methylation levels of 3 genes—Wif1, PENK, and NPY—were tied to CRC-associated colon microbe changes. In a separate cohort of 1,000 people, patients with CRC exhibited higher CMI for these 3 genes, compared with healthy controls.
Metagenomic analysis revealed that the abundance of some bacterial species, such as Parvimonas, was directly associated with increased blood CMI.
According to the authors, alterations in colon-associated microbes may trigger DNA methylation changes that promote CRC, raising the possibility that changes in gut microbes and DNA methylation may serve as potential biomarkers of CRC.
Colorectal cancer epigenetic signatures is linked to microbiota
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