Abstract
Periodontal disease is a microbially-mediated inflammatory disease of tooth-supporting tissues that leads to bone and tissue loss around teeth. Although bacterially-mediated mechanisms of alveolar bone destruction have been widely studied, the effects of a polymicrobial infection on the periodontal ligament and microbiome/virome have not been well explored. Therefore, the current investigation introduced a new mouse model of periodontal disease to examine the effects of a polymicrobial infection on periodontal ligament (PDL) properties, changes in bone loss, the host immune response, and the microbiome/virome using shotgun sequencing. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Fusobacterium nucleatum were used as the polymicrobial oral inoculum in BALB/cByJ mice. The polymicrobial infection triggered significant alveolar bone loss, a heightened antibody response, an elevated cytokine immune response, a significant shift in viral diversity and virome composition, and a widening of the PDL space; the latter two findings have not been previously reported in periodontal disease models. Changes in the PDL space were present at sites far away from the site of insult, indicating that the polymicrobial radius of effect extends beyond the bone loss areas and site of initial infection and wider than previously appreciated. Associations were found between bone loss, specific viral and bacterial species, immune genes, and PDL space changes. These findings may have significant implications for the pathogenesis of periodontal disease and biomechanical properties of the periodontium. This new polymicrobial mouse model of periodontal disease in a common mouse strain is useful for evaluating the features of periodontal disease.
Highlights
Periodontitis is an inflammatory disease triggered by a microbial dysbiosis that affects the supporting tissues around teeth and it eventually leads to tooth loss if left untreated
Among the biofilm-associated microbiota, several bacterial species are highly associated with periodontal disease; namely Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia
Several different mouse models of periodontal disease that mimic the human condition have been proposed in the literature, including ligature models[35,36], injection models[37,38], monoinfection models inoculated with only one strain of bacteria[39,40,41,42], and even polymicrobial infection models[43,44,45]
Summary
Periodontitis is an inflammatory disease triggered by a microbial dysbiosis that affects the supporting tissues around teeth and it eventually leads to tooth loss if left untreated. Nucleatum can coaggregate with a significant number of bacteria in the oral cavity and is thought to be an important “microbial bridge” during dental plaque formation[14,15] These pathogenic bacteria contribute to periodontal disease via a variety of mechanisms, including through secretion of proteolytic enzymes or proteases[16], activation and modulation of the host immune response via bacterial LPS and other surface effector molecules[17,18], and invasion of host cells[19]. After 8 weeks of inoculation and infection with the periodontal pathogens, mice exhibited significantly more alveolar bone loss (0.136 mm ± 0.011) compared to the control group (0.088 mm ± 0.004) (Fig. 4a, b). Specific viral and bacterial species were associated with bone loss in mice with the polymicrobial infection (Fig. 7a–h; Table 3). There were weaker associations between bacteria/virus species and PDL space (Supplemental Fig. 2)
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