The role of the microbiota in periodontal disease

Periodontal disease is the most frequent cause of tooth loss in humans and is the most prevalent disease associated with bone loss, including osteoporosis. Periodontal destruction is initiated by bacteria that colonize the tooth surface, leading to inflammation and bone resorption. To assess the roles of IL-1 and TNF in this process, studies were conducted in a Macaca fascicularis primate model of experimental periodontitis. Function-blocking soluble receptors to IL-1 and TNF were applied by local injection to sites with induced periodontal destruction and compared with similar sites injected with vehicle alone. The results indicate that injection of soluble receptors to IL-1 and TNF inhibited by approximately 80% the recruitment of inflammatory cells in close proximity to bone. The formation of osteoclasts was reduced by 67% at the experimental sites compared with that at the control sites, and the amount of bone loss was reduced by 60%. All results were statistically significant (p < 0.01). These findings indicate that a significant component of the pathologic process of periodontitis is due to IL-1/TNF activity, since inhibiting IL-1/TNF reduces both inflammatory cell recruitment and bone loss. The data also suggest that inflammation associated with gingivitis is actively protective, since blocking further up-regulation of the host response with IL-1/TNF inhibitors does not cause periodontal damage. Furthermore, these results coupled with recent evidence that IL-1 and TNF participate in endocrine-associated osteoporosis suggest that multiple pathologies involving excessive loss of bone may operate through a common mechanism involving IL-1 and/or TNF.

High-throughput 16S rRNA gene sequencing has allowed the characterization of subgingival microbiome shifts from health to periodontitis identifying health-associated, periodontitis-associated and core species, which preserve their proportions from health to disease. The development of gingivitis is also characterized by distinct shifts. Microbiome shifts resemble microbial successions and result from interspecies interactions and community adaptation to the changing environment as inflammation ensues. Gingivitis-associated and core species are proposed as likely mediators of microbiome transitions.

To examine the global effects of Mycobacterium tuberculosis (M. tuberculosis) infection on macrophages. The gene expression profiling of macrophage U937, in response to infection with M. tuberculosis H(37)R(a), was monitored using a high-density cDNA microarray. M. tuberculosis infection caused 463 differentially expressed genes, of which 366 genes are known genes registered in the Gene Bank. These genes function in various cellular processes including intracellular signalling, cytoskeletal rearrangement, apoptosis, transcriptional regulation, cell surface receptors, cell-mediated immunity as well as a variety of cellular metabolic pathways, and may play key roles in M. tuberculosis infection and intracellular survival. M. tuberculosis infection alters the expression of host-cell genes, and these genes will provide a foundation for understanding the infection process of M. tuberculosis. The cDNA microarray is a powerful tool for studying pathogen-host cell interaction.