The microbiome and host methylome profiles of MV DNA were analysed using 16S rRNA sequencing and methylated DNA immunoprecipitation sequencing (MeDIP-seq), respectively.<h4>Results</h4>The periodontitis group showed increased CD63+, CD45+, CD29<sup>+</sup> and CD24<sup>+</sup> MV subpopulations (AUC > 0.7), along with significantly higher bacterial outer membrane vesicles (AUC > 0.89) from Treponema, Fretibacterium and Treponema denticola, compared to both healthy and gingivitis groups, as well as the non-periodontitis (combining healthy and gingivitis) group. Here, CD63 is linked to periodontitis.