Altered microRNA expression correlates with reduced TLR2/4-dependent periodontal inflammation and bone resorption induced by polymicrobial infection

Periodontitis is the most prevalent chronic immuno-infectious multispecies dysbiotic disease of the oral cavity. The Toll-like receptors (TLRs) provide the first line of defense, one of the best-characterized pathogen detection systems, and play a vital role in recognizing multiple microbial products. Multispecies infection with periodontal bacteria <i>Streptococcus gordonii</i>, <i>Fusobacterium nucleatum</i>, <i>Porphyromonas gingivalis</i>, <i>Treponema denticola</i>, and <i>Tannerella forsythia</i> induced gingival inflammation, alveolar bone resorption (ABR), and microRNA (miRNA) expression in the C57BL6/J wild-type mice, whereas infection did not significantly increase ABR in the TLR2/4 deficient mice. Among the 15 miRNAs investigated, miR-146a-5p and miR-15a-5p were upregulated in wild-type and TLR2^-/- mice, and miR-146a-5p, miR-30c-5p, and let-7c-5p were upregulated in the TLR4^-/- mice compared to sham-infected controls. Notably, the inflammatory miRNA miR-146a-5p was uniquely upregulated among the wild-type and TLR2^-/- mice but not in the TLR4^-/- mice. The upregulated miRNAs (miR-146a, miR-15-a-5p, let-7c-5p) and downregulated miRNAs could be candidate biomarkers for oral bacteria and TLRs-mediated induction of periodontitis if they are confirmed in large-scale human studies.