Polymicrobial periodontal disease triggers a wide radius of effect and unique virome

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.

The oralome and its dysbiosis: New insights into oral microbiome-host interactions

“…However, only few studies have evaluated the oral viral community [43] , [44] , [45] , [48] , [49] and, thus, more studies are still necessary to evaluate the role of the virome in the oral microbiome.…”

“…Recently, our group introduced a new polymicrobial mouse model of periodontal disease in a common mouse strain (BALB/cBy), which revealed a widening of the periodontal ligament space, alveolar bone loss, and an increased host immune response after a polymicrobial infection [49] . This model may be useful for assaying microbial biofilm interactions in vivo .…”

The Post-hunter-gatherer Era Microbes Hypothesis for Chronic Inflammatory Diseases

“…However, to be most useful, all relevant PHMs and opportunistic infections would need to be considered. This perspective is in accord with the increasing recognition of the importance of polymicrobial infections [24,54,326,327].…”

Periodontal inflammation triggers a site‐specific and wide radius of calcium metabolic effects on alveolar bone

“…However, some studies have shown a thinning of the cortical plates, observed as hard lines on radiographs, and the expansion of the PDL in the root apex and interradicular regions (regions far removed from the site of insult) as clinically important evidence of periodontal disease 57,58 . Furthermore, we recently reported that periodontal disease induced by a polymicrobial infection in mice caused PDL expansion beyond the site of bone loss, which was far from the site of initial bacterial infection 59 . In the present study, the number of TRAP‐positive cells increased in areas distant from the ligated site compared to the controls, whereas BAP expression was maintained in the resorption lacunae of the alveolar bone.…”