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Recently, an intestinal dysbiotic microbiota with enrichment in oral cavity bacteria has been described in colorectal cancer (CRC) patients. Here, we characterize and investigate 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 with 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 show that  P. micra  phylotype A alters the DNA methylation profile promoters of key tumor-suppressor genes, oncogenes, and genes involved in epithelial–mesenchymal transition. In colonic mucosa of CRC patients carrying  P. micra  phylotype A, we found similar DNA methylation alterations, together with significant enrichment of differentially expressed genes in pathways involved in inflammation, cell adhesion, and regulation of actin cytoskeleton, providing evidence of  P. micra’s  possible role in the carcinogenic process.

Parvimonas micra , an oral pathobiont associated with colorectal cancer, epigenetically reprograms human colonocytes