Generalized Aggressive Periodontitis - A Periodontal Chimera

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Objectives: Periodontitis is a disease of the surrounding tissues of the tooth (periodontium) in which the destruction leads to weakening of the tooth support and eventual tooth loss. Approximately 46% of adults in the US suffer from this disease.1 The current classification of periodontal diseases and conditions recognizes 3 forms of periodontitis: Chronic periodontitis (CP), Localized Aggressive Periodontitis (LAP), and Generalized Aggressive Periodontitis (GAP). All three are inflammatory conditions that are microbial in nature. GAP is considered the most destructive of the three conditions due to its rapid destruction of the periodontium and its wide distribution in the mouth. Previous close-ended approaches to examine the bacterial constituents of the 3 diseases were equivocal, however, the consensus is that CP and GAP are considered polymicrobial in nature, while LAP is attributed to a mono-infection of the bacterial species Aggregatibacter actinomycetemcomitans.2 Since evidence is emerging that taxonomically distinct periodontal biofilms are functionally congruent, the present investigation sought to characterize the functional potential within the subgingival bacteria of CP, GAP and LAP. Methods: Subgingival plaque samples were collected from deep and shallow sites of 25 patients with CP, 17 with GAP, and 17 with LAP. Whole-genome shotgun DNA sequencing was used to characterize the functions encoded in these microbial communities. Sequences were analyzed using the MG-RAST pipeline for subsystem classification, and Kraken for taxonomic identification. Organismal diversity and functional abundances were compared between groups using dissimilarity indices, differential abundance metrics and network analysis. Results: 11.5 million sequences per sample contributed to 5973 functionally annotated genes. Principal coordinate analysis revealed distinct clustering of the three diseases based on community membership, structure and functional potential (p<0.05, ANOSIM). GAP separated the distances between LAP and CP, concordant with concept of a mixed infection of the two diseases. GAP and CP had similar functions of fermentation, phage transfer, while GAP and LAP had similar virulence factors. Taxonomic analysis revealed the polymicrobial nature of all three conditions. Network analysis showed similar inter-bacterial interaction networks between GAP and LAP, with similar membership of Treponema denticola, Filifactor alocis, Tannerella forsythia and Porphyromonadaceae Spp. Implications: This is the first time that the three disease entities are shown to exist as a continuum rather than discrete disease entities. This paradigm shift in has major implications on the classification of disease. That is, the aggressive but localized nature of LAP is globalized to the entire periodontal tissues by the superimposition of CP. Moreover, these findings cast doubt on current empirical treatment protocols for GAP that follow closely the protocols made for LAP. Finally, the breadth of the microbial members in LAP extend beyond the single bacteria species which greatly expands our understanding of the disease.


Health Sciences: 1st Place (The Ohio State University Edward F. Hayes Graduate Research Forum)


metagenomics, periodontics, microbiology, bioinformatics, aggressive periodontitis, dentistry