Periodontal disease depends on the presence of different microorganisms in the oral cavity that during the colonization of periodontal tissues form a multispecies biofilm community, thus allowing them to survive under adverse conditions or facilitate further colonization of host tissues. Not only numerous bacterial species participate in the development of biofilm complex structure but also fungi, especially Candida albicans, that often commensally inhabits the oral cavity. C. albicans employs an extensive armory of various virulence factors supporting its coexistence with bacteria resulting in successful host colonization and propagation of infection. In this article, we highlight various aspects of individual fungal virulence factors that may facilitate the collaboration with the associated bacterial representatives of the early colonizers of the oral cavity, the bridging species, and the late colonizers directly involved in the development of periodontitis, including the “red complex” species. In particular, we discuss the involvement of candidal cell surface proteins—typical fungal adhesins as well as originally cytosolic “moonlighting” proteins that perform a new function on the cell surface and are also present within the biofilm structures. Another group of virulence factors considered includes secreted aspartic proteases (Sap) and other secreted hydrolytic enzymes. The specific structure of the candidal cell wall, dynamically changing during morphological transitions of the fungus that favor the biofilm formation, is equally important and discussed. The non-protein biofilm-composing factors also show dynamic variability upon the contact with bacteria, and their biosynthesis processes could be involved in the stability of mixed biofilms. Biofilm-associated changes in the microbe communication system using different quorum sensing molecules of both fungal and bacterial cells are also emphasized in this review. All discussed virulence factors involved in the formation of mixed biofilm pose new challenges and influence the successful design of new diagnostic methods and the application of appropriate therapies in periodontal diseases.

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The Role of Candida albicans Virulence Factors in the Formation of Multispecies Biofilms With Bacterial Periodontal Pathogens

ABSTRACT Background Periodontitis is a chronic multifactorial inflammatory disease. Porphyromonas gingivalis is a primary periopathogen in the initiation and development of periodontal disease. Evidence has shown that P. gingivalis is associated with systemic diseases, including IBD and fatty liver disease. Inflammatory response is a key feature of diseases related to this species. Methods C57BL/6 mice were administered either PBS, or P. gingivalis. After 9 weeks, the inflammatory response in gut, spleen, and liver was analyzed. Results The findings revealed significant disturbance of the intestinal microbiota and increased inflammatory factors in the gut of P. gingivalis-administered mice. Administrated P. gingivalis remarkably promoted the secretion of IRF-1 and activated the inflammatory pathway IFN-γ/STAT1 in the spleen. Histologically, mice treated with P. gingivalis exhibited hepatocyte damage and lipid deposition. The inflammatory factors IL-17a, IL-6, and ROR-γt were also upregulated in the liver of mice fed with P. gingivalis. Lee’s index, spleen index, and liver index were also increased. Conclusion These results suggest that administrated P. gingivalis evokes inflammation in gut, spleen, and liver, which might promote the progression of various systemic diseases.

https://www.tandfonline.com/doi/pdf/10.1080/20002297.2022.2088936?needAccess=true

Inflammatory response of gut, spleen, and liver in mice induced by orally administered Porphyromonas gingivalis

Aim To compare the risk of gingival and periodontal diseases (GPD) between ever users and never users of metformin in patients with type 2 diabetes mellitus. Methods The Taiwan’s National Health Insurance database was used to enroll 423,949 patients with new onset diabetes mellitus from 1999 to 2005. After excluding ineligible patients, 60,309 ever users and 5578 never users were followed up for the incidence of GPD from January 1, 2006 until December 31, 2011. Propensity score-weighted hazard ratios were estimated by Cox regression. Results GPD was newly diagnosed in 18,528 ever users (incidence: 7746.51 per 100,000 person-years) and 2283 never users (incidence: 12158.59 per 100,000 person-years). The hazard ratio that compared ever users to never users was 0.627 (95% confidence interval: 0.600-0.655). When metformin use was categorized by tertiles of cumulative duration and cumulative dose, the risk significantly reduced in a dose-response pattern when the cumulative duration reached approximately 2 years or the cumulative dose reached 670 grams. Analyses on the tertiles of defined daily dose of metformin showed that the reduction of GPD risk could be seen in all three subgroups but the benefit would be greater when the daily dose increased. Conclusion Long-term use of metformin is associated with a significantly reduced risk of GPD.

Metformin and risk of gingival/periodontal diseases in diabetes patients: A retrospective cohort study

BACKGROUND AND OBJECTIVE
The translocation of oral bacteria, including Porphyromonas gingivalis, to the gut has been shown to alter gut microbiome. However, the effect of P. gingivalis on gut microbiome in relation to aging has not been demonstrated. We hypothesize that P. gingivalis has more detrimental effect on gut environment with increased age. The objective of this study is to investigate the effect of P. gingivalis on gut environment using aged mice.


MATERIALS AND METHODS
C57BL/6J mice aged 4 weeks (young) or 76 weeks (old) were divided into four groups: control-young, control-old, P. gingivalis-administered young, and P. gingivalis-administered old. P. gingivalis was orally administered thrice weekly for 5 weeks. At 30 days after the last P. gingivalis administration, 16S rRNA sequencing was performed to study the gut microbiome. The mRNA and protein expression of intestinal junctional barrier molecules and the levels of the inflammatory cytokines IL-1β and TNF-α in the serum were evaluated.


RESULTS
Significant differences in the gut microbiomes between the groups, in terms of taxonomic abundance, bacterial diversity, and predicted metagenome function, were observed. A significant reduction in the alpha diversity and in the abundance of beneficial bacteria, such as Akkermansia and Clostridiaceae, in the P. gingivalis-administered old mice was observed. The mRNA and protein levels of Claudin-1 and Claudin-2 in the intestine were significantly elevated, while E-cadherin was significantly downregulated in the P. gingivalis-administered old mice, as were the serum levels of IL-1β and TNF-α.


CONCLUSION
The effect of P. gingivalis on the gut environment is more pronounced in old mice than in young mice.

The effect of Porphyromonas gingivalis on the gut microbiome of mice in relation to aging.

Many articles describe in detail local accidents and complications in the treatment of dental implants. The comparison of the data provided is not always correct, because different criteria and indexes were used in different classifications. The problem of inflammatory complications of dental implantation is particularly acute, in the long term after prosthetics in patients who have facial mucositis and peri-implantitis. This observation gave rise to a hygienic hypothesis, which postulates that 

Influence of interdental hygiene products on periodontal pathogens according to indicators of hygienic indices

Periodontal disease, a common inflammatory disease, is considered a hazardous factor that contributes to the development of diseases of the digestive system as well as other systems. The bridge between periodontitis and systemic diseases is believed to be periodontal pathogens. The intestine, as part of the lower gastrointestinal tract, has a close connection with the oral cavity. Within the intestine, the intestinal barrier acts as a multifunctional system including microbial, mucous, physical and immune barrier. The intestinal barrier forms the body’s first line of defense against external pathogens; its breakdown can lead to pathological changes in the gut and other organs or systems. Reports in the literature have described how oral periodontal pathogens and pathobiont-reactive immune cells can transmigrate to the intestinal mucosa, causing the destruction of intestinal barrier homeostasis. Such findings might lead to novel ideas for investigating the relationship between periodontal disease and other systemic diseases. This review summarizes studies on the effects of periodontal pathogens on the intestinal barrier, which might contribute to understanding the link between periodontitis and gastrointestinal diseases.

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Jiaqi Wang

Papers

Multifaceted Impacts of Periodontal Pathogens in Disorders of the Intestinal Barrier