Dynamic Changes in the Subgingival Microbiome and Their Potential for Diagnosis and Prognosis of Periodontitis

Abstract

The human microbiome influences and reflects the health or disease state of the host. Periodontitis, a disease affecting about half of American adults, is associated with alterations in the subgingival microbiome of individual tooth sites. Although it can be treated, the disease can reoccur and may progress without symptoms. Without prognostic markers, follow-up examinations are required to assess reoccurrence and disease progression and to determine the need for additional treatments. To better identify and predict the disease progression, we aim to determine whether the subgingival microbiome can serve as a diagnosis and prognosis indicator. Using metagenomic shotgun sequencing, we characterized the dynamic changes in the subgingival microbiome in periodontitis patients before and after treatment at the same tooth sites. At the taxonomic composition level, the periodontitis-associated microorganisms were significantly shifted from highly correlated in the diseased state to poorly correlated after treatment, suggesting that coordinated interactions among the pathogenic microorganisms are essential to disease pathogenesis. At the functional level, we identified disease-associated pathways that were significantly altered in relative abundance in the two states. Furthermore, using the subgingival microbiome profile, we were able to classify the samples to their clinical states with an accuracy of 81.1%. Follow-up clinical examination of the sampled sites supported the predictive power of the microbiome profile on disease progression. Our study revealed the dynamic changes in the subgingival microbiome contributing to periodontitis and suggested potential clinical applications of monitoring the subgingival microbiome as an indicator in disease diagnosis and prognosis.

Resolvin E1 Reverses Experimental Periodontitis and Dysbiosis

“…Therefore, the diseased microbial community is more diverse at any one site (alpha diversity) than is the healthy microbial community. The microbial community of samples from different disease sites becomes more similar (beta diversity) compared to the microbial community of different healthy samples (59–63). The ecological plaque hypothesis proposed by Marsh (64, 65) emphasizes a direct link between local environmental conditions and the activity and composition of the microbial community.…”

Comparative metagenomics reveals taxonomically idiosyncratic yet functionally congruent communities in periodontitis

“…There have been several investigations in recent years that have examined the functional potential of the subgingival microbiome in health and disease1213144049. While some of these investigations have used a targeted DNA-array based approach to examine selected functions14, others have been limited by small sample sizes in making statistical comparisons12134049.…”

“…While some of these investigations have used a targeted DNA-array based approach to examine selected functions14, others have been limited by small sample sizes in making statistical comparisons12134049. Moreover, all of these studies have focused only on the bacteriome.…”

“…While the taxonomic profiles of eubiotic and dysbiotic periodontal communities are well-studied789101112131415, little is known about their genome signatures, and whether community level functional alterations accompany compositional shifts in the transition to and in the state of disease. Even less is known about the selection pressures exerted by a disease-associated environment on the pre-existing microbiome.…”

Pro-resolving mediators in the regulation of periodontal disease

“…In active disease, species that are associated with disease clinically overgrow due to inflammation-induced changes in the local ecology obtaining required nutrients. The disease associated microbial community becomes more diverse in diseased sites (α diversity), while the microbial composition of diseased site within the individual become more similar (β diversity) (67–71). These results emphasize two important biological principles: 1. there is a direct link between local environmental conditions and the activity and composition of the microbiota, and 2. the inflammation induced impact on the microbiome is modifiable by active resolution of inflammation.…”