Parvimonas micra, an oral pathobiont associated with colorectal cancer, epigenetically reprograms human primary intestinal epithelial cells

Abstract

SummaryRecently, an intestinal dysbiotic microbiota in the feces of colorectal cancer (CRC) patients with an enrichment of bacteria belonging to the oral microbiota has been described. Here we characterized and investigated one of these oral pathobionts, the Gram-positive anaerobic coccus Parvimonas micra. We identified two phylotypes (A and B) exhibiting different phenotypes and adhesion capabilities. We observed a strong association of phylotype A with CRC, with its higher abundance in feces and in tumoral tissue compared to the normal homologous colonic mucosa, which was associated with a distinct methylation status of patients. By developing an in vitro hypoxic co-culture system of human primary colonic cells with anaerobic bacteria, we showed that P. micra phylotype A induces modifications in DNA methylation of the promoters of several tumor-suppressor genes, oncogenes, and genes involved in epithelial-mesenchymal transition, providing evidence of its possible role in carcinogenesis.