It was found that periodontitis-derived virulence factors can selectively localize to β-cells27 and induce the emergence of bihormonal cells (Fig. 3) through epigenetic modifications, such as reducing the abundance of histone 3 trimethylated at lysine 4 (H3K4me3)67 and decreasing DNA methyltransferase 1 (DNMT1),68–70 to downregulate the β-cell-specific transcription factors PDX1 and NK6 homeobox 1 (NKX6.1)71 and induce the development of bihormonal cells. This evidence concerns the gene NKX6-1 and periodontitis.