These methylated genes were enriched in inflammation-related pathways, including AMP-activated protein kinase (AMPK) and Toll-like receptor 4 (TLR4) pathways.<h4>Conclusion</h4>This exploratory study found that host methylome and microbiome profiles in salivary MVs reflect periodontal disease status, and hence supports their potential as non-invasive liquid biopsy biomarkers for periodontitis. Here, TLR4 is linked to periodontal disorder.