Dysbiotic Biofilms Deregulate the Periodontal Inflammatory Response

Abstract

Periodontal diseases originate from a dysbiosis within the oral microbiota, which is associated with a deregulation of the host immune response. Although little is known about the initiation of dysbiosis, it has been shown that HO production is one of the main mechanisms by which some commensal bacteria suppress the outgrowth of pathobionts. Current models emphasize the critical nature of complex microbial biofilms that form unique microbial ecologies and of their change during transition from health (homeostatic) to disease (dysbiotic). However, very little is known on how this alters their virulence and host responses. The objective of this study was to determine differences in virulence gene expression by pathobionts and the inflammatory host response in homeostatic and dysbiotic biofilms originating from the same ecology. Quantitative polymerase chain reaction was performed to quantify the pathobiont outgrowth. Expression analysis of bacterial virulence and cellular inflammatory genes together with cytokine enzyme-linked immunosorbent assays were used to detect differences in bacterial virulence and to analyze potential differences in inflammatory response. An increase in pathobionts in induced dysbiotic biofilms was observed compared to homeostatic biofilms. The main virulence genes of all pathobionts were upregulated in dysbiotic biofilms. Exposure of these dysbiotic biofilms to epithelial and fibroblast cultures increased the expression of interleukin (IL)-6, IL-1β, tumor necrosis factor-α, and matrix metalloprotease 8, but especially the chemokine CXCL8 (IL-8). Conversely, homeostatic and beneficial biofilms had a minor immune response at the messenger RNA and protein level. Overall, induced dysbiotic biofilms enriched in pathobionts and virulence factors significantly increased the inflammatory response compared to homeostatic and commensal biofilms.

Antimicrobial function of the polyunsaturated fatty acid KetoC in an experimental model of periodontitis

“…‒ In addition, an increase in P. gingivalis is associated with the pathogenesis of periodontitis . Another in vitro study showed an elevated abundance of this Gram‐negative anaerobic bacterium in dysbiotic biofilm, stimulating the production of inflammatory genes . Based on this strong evidence, in the present study, we developed a mouse model of periodontitis by placement of a ligature and administration of P. gingivalis .…”

Macrophage immunomodulation in chronic osteolytic diseases—the case of periodontitis

“…Inflammation drives extracellular matrix degradation and bone resorption, but the question how these processes are related in the onset and progression of disease remains unanswered. Pathogenic but not commensal bacteria in dysbiotic biofilms deregulate periodontal inflammatory responses that favor pro‐osteolytic environments characterized by release of cytokines and matrix degrading enzymes that mediate the breakdown of connective tissue . Considerable attention has been paid to Porphyromonas gingivalis , Treponema denticola , Tannerella forsythia , and Aggregatibacter actinomycetemcomitans , which were linked to both chronic and aggressive forms of PD.…”

“…Pathogenic but not commensal bacteria in dysbiotic biofilms deregulate periodontal inflammatory responses that favor pro-osteolytic environments characterized by release of cytokines and matrix degrading enzymes that mediate the breakdown of connective tissue. 22 Considerable attention has been paid to Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans, which were linked to both chronic and aggressive forms of PD. However, the complex interactions between these keystone periodontal pathogens and dysbiotic subgingival biofilms are beginning to emerge as important factors driving pathogenicity in susceptible individuals.…”

Current understanding of periodontal disease pathogenesis and targets for host‐modulation therapy

“…In the gingival crevice/pocket, these inflammatory spoils can be used as nutrients to fuel the selective expansion of a subset of bacterial species (eg, proteolytic and asaccharolytic pathobionts), thereby exacerbating the imbalance of the microbiota (dysbiosis) . In this regard, the addition of serum, hemoglobin, or hemin to an in vitro‐generated oral multispecies community selectively induces the outgrowth of pathobionts, which interestingly upregulate genes that encode proteases, hemolysins, and molecules involved in hemin acquisition . This conversion of the original “homeostatic” community into a “dysbiotic” one can also increase the community's proinflammatory potential .…”