ABSTRACT Periodontal disease is mediated by the dynamic interplay between host inflammation and changes in subgingival biofilm community composition. The keystone pathogen, Porphyromonas gingivalis is known to subvert the immune response to promote inflammation and favorable conditions for pathobiont organisms, while inhibiting immune system clearance of bacteria. Because of this, P. gingivalis has been proposed to initiate periodontal disease. Here we propose a new paradigm for the initiation of periodontal disease, mediated at the gingival margin by long filamentous cells that bring plaque organisms into close or direct contact with the epithelium to initiate inflammation in the form of gingivitis. This reversible inflammatory state then induces dysbiosis in the subgingival community. We will test our hypothesis by imaging intact biofilms on extracted teeth involved in gingivitis and periodontitis, including the biofilm at the gingival margin with FISH probes for up to 18 different taxa. We will further perform quantitative comparative structural analyses of periodontitis associated human biofilms and canine models to specifically identify conserved structural features of pathogenic subgingival biofilms. Lastly, we will map the spatial location of differentially expressed genes within filamentous cells in plaque biofilms when these cells are in direct or close contact with specific partner species. This work will comprise a holistic approach to identify structure-function relationships in healthy and periodontal disease-associated biofilms that underly periodontal disease initiation and progression.