Filifactor alocis promotes a dysbiotic state, inflammation, and alveolar bone loss in a TLR2-dependent manner

Enrichment of the oral microorganism Filifactor alocis is strongly associated with the progression of periodontitis. However, F. alocis is part of a complex dysbiotic microbial community, and the organism's direct pathogenic potential remains uncharacterized. Using the oral gavage model of experimental periodontitis, we revealed that F. alocis promotes alveolar bone loss. Furthermore, F. alocis infection induced significant overexpression of pro-inflammatory markers associated with osteoclastogenesis and inflammation in oral tissues. Interestingly, despite colonizing in low abundance, F. alocis infection promoted the perturbation of the indigenous oral microbial community towards a dysbiotic state. Systemically, high levels of pro-inflammatory cytokines, chemokines, and antibody titers against F. alocis were detected in the sera of infected animals. Mechanistically, we demonstrate that F. alocis requires TLR2 to display its pathogenic potential. These findings identify F. alocis as an oral pathogen that can disrupt the homeostatic relationship between the host and the indigenous microbiome causing inflammation and bone resorption. Our findings provide novel insights into the pathogenic potential of F. alocis in periodontitis.