Pathogens

Editorial

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Open AccessEditorial

Editorial for the Special Issue: Oral Immunology and Periodontitis

by Ulvi K. Gürsoy

Pathogens 2022, 11(5), 564; https://doi.org/10.3390/pathogens11050564 - 10 May 2022

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Abstract

The two most common forms of oral infectious diseases are caries and periodontal diseases [...] Full article

(This article belongs to the Special Issue Oral Immunology and Periodontitis)

Research

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10 pages, 427 KiB

Open AccessFeature PaperArticle

Evaluation of Gene Polymorphism and Gingival Crevicular Fluid Levels of Matrix Metalloproteinase-3 in a Group of Turkish Periodontitis Patients

by Gökhan Kasnak, Mustafa Yılmaz, Revan Birke Koca Ünsal, Nuray Gürel Polat and Erhan Fıratlı

Pathogens 2021, 10(10), 1260; https://doi.org/10.3390/pathogens10101260 - 29 Sep 2021

Cited by 5 | Viewed by 1632

Abstract

Introduction: Periodontitis is characterized by the destruction of tooth-supporting tissues. Matrix metalloproteinases (MMPs) play a significant part in the degradation of collagen structure. The gingival crevicular fluid (GCF) levels of MMPs increase with the progression of periodontal inflammation. Polymorphisms can be responsible for [...] Read more.

Introduction: Periodontitis is characterized by the destruction of tooth-supporting tissues. Matrix metalloproteinases (MMPs) play a significant part in the degradation of collagen structure. The gingival crevicular fluid (GCF) levels of MMPs increase with the progression of periodontal inflammation. Polymorphisms can be responsible for high expression of MMPs and can exacerbate the breakdown of collagen structure. This study aims to investigate the effect of MMP-3 -1171 5A/6A polymorphism and the GCF levels of MMP-3 in a group of Turkish periodontitis patients. Materials and Methods: Non-smoking, stage II grade A periodontitis (S II-Gr A) (n = 68) and stage II grade B periodontitis (S II-Gr C) (n = 64) patients were recruited. Healthy individuals (H) (n = 72) without signs of gingivitis or periodontitis served as the control. Venous blood was collected from participants to obtain DNA, and the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method was used to detect polymorphism. GCF samples were taken to assess MMP-3 levels using an enzyme-linked immunosorbent assay (ELISA). Results: The MMP-3 -1179 5A/6A distribution showed no significant difference between the groups (p > 0.05). However, the MMP-3 GCF levels of the S II-Gr C group were higher than those of both the S II-Gr A and H groups (p < 0.05), and elevated MMP-3 levels were detected in S II-Gr A compared to H (p < 0.05). Conclusion: The MMP-3 GCF levels showed an association with periodontal tissue destruction, although single nucleotide polymorphism was not associated with the S II-Gr C and S II-Gr A groups in the Turkish population. Full article

(This article belongs to the Special Issue Oral Immunology and Periodontitis)

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7 pages, 778 KiB

Open AccessCommunication

Regulation of hBD-2, hBD-3, hCAP18/LL37, and Proinflammatory Cytokine Secretion by Human Milk Oligosaccharides in an Organotypic Oral Mucosal Model

by Ulvi K. Gürsoy, Krista Salli, Eva Söderling, Mervi Gürsoy, Johanna Hirvonen and Arthur C. Ouwehand

Pathogens 2021, 10(6), 739; https://doi.org/10.3390/pathogens10060739 - 11 Jun 2021

Cited by 10 | Viewed by 2921

Abstract

Human milk oligosaccharides (HMOs), the third largest solid fraction in human milk, can modulate inflammation through Toll-like receptor signaling, but little is known about their immunomodulatory potential in the oral cavity. In this study, we determined whether the HMOs 2′-fucosyllactose (2′-FL) and 3-fucosyllactose [...] Read more.

Human milk oligosaccharides (HMOs), the third largest solid fraction in human milk, can modulate inflammation through Toll-like receptor signaling, but little is known about their immunomodulatory potential in the oral cavity. In this study, we determined whether the HMOs 2′-fucosyllactose (2′-FL) and 3-fucosyllactose (3-FL) regulate human-beta defensin (hBD)-2 and -3, cathelicidin (hCAP18/LL-37), and cytokine responses in human gingival cells using a three-dimensional oral mucosal culture model. The model was incubated with 0.1% or 1% 2′-FL and 3-FL, alone and in combination, for 5 or 24 h, and hBD-2, hBD-3, and hCAP18/LL-37 were analyzed by immunohistochemistry. The expression profiles of interleukin (IL)-1, IL-1RA, IL-8, and monocyte chemoattractant protein (MCP)-1 were determined by LUMINEX immunoassay. The combination of 1% 2′-FL and 1% 3-FL, and 1% 3-FL alone, for 24 h upregulated hBD-2 protein expression significantly (p < 0.001 and p = 0.016, respectively). No changes in the other antimicrobial peptides or proinflammatory cytokines were observed. Thus, 3-FL, alone and in combination with 2′-FL, stimulates oral mucosal secretion of hBD-2, without effecting a proinflammatory response when studied in an oral mucosal culture model. Full article

(This article belongs to the Special Issue Oral Immunology and Periodontitis)

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23 pages, 3828 KiB

Open AccessArticle

Impact of Probiotics on the Salivary Microbiota and Salivary Levels of Inflammation-Related Proteins during Short-Term Sugar Stress: A Randomized Controlled Trial

by Christine Lundtorp-Olsen, Christian Enevold, Claus Antonio Juel Jensen, Steen Nymann Stofberg, Svante Twetman and Daniel Belstrøm

Pathogens 2021, 10(4), 392; https://doi.org/10.3390/pathogens10040392 - 25 Mar 2021

Cited by 9 | Viewed by 2967

Abstract

Background: The purpose of the present investigation was to characterize the effect of probiotics on the composition of the salivary microbiota and salivary levels of inflammation-related proteins during short-term sugar stress. We tested the hypotheses that consumption of probiotics may partly counteract the [...] Read more.

Background: The purpose of the present investigation was to characterize the effect of probiotics on the composition of the salivary microbiota and salivary levels of inflammation-related proteins during short-term sugar stress. We tested the hypotheses that consumption of probiotics may partly counteract the detrimental influence of sugar stress on oral homeostasis. Methods: The present study was a five-week, blinded, randomized controlled trial with four study arms—A: sucrose and probiotic (n = 20); B: sucrose and placebo (n = 20); C: xylitol and probiotic (n = 20); D: xylitol and placebo (n = 20). Saliva samples were collected at baseline and after two and five weeks. The salivary microbiota was characterized by means of 16S rDNA sequencing, and sequences were referenced against the Human Oral Microbiome Database (HOMD). Neutrophil gelatinase-associated lipocalin (NGAL) and transferrin levels were quantified using immunoassays. Results: Sugar stress induced a significant increase in the relative abundance of the genus Streptococcus from 29.8% at baseline to 42.9% after two weeks. Changes were transient and were completely reversed three weeks after discontinuation of sugar stress. Xylitol and probiotics alone had no effect on the salivary microbiota, whereas the combination of xylitol and probiotics induced a significant decrease in the relative abundance of Streptococcus species from 37.6% at baseline to 23.0% at week 2. Sugar stress significantly increased salivary transferrin levels, and the effect was partly counteracted by concomitant use of probiotics. Conclusions: The data clearly demonstrate an impact of combined consumption of xylitol and probiotics on the composition of the salivary microbiota. Future studies are needed to evaluate whether the combined use of xylitol and the probiotic strains tested could have clinically protective effects during periods of sugar stress. Full article

(This article belongs to the Special Issue Oral Immunology and Periodontitis)

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19 pages, 2827 KiB

Open AccessArticle

Probiotics Do Not Alter the Long-Term Stability of the Supragingival Microbiota in Healthy Subjects: A Randomized Controlled Trial

by Christine Lundtorp-Olsen, Christian Enevold, Svante Twetman and Daniel Belstrøm

Pathogens 2021, 10(4), 391; https://doi.org/10.3390/pathogens10040391 - 24 Mar 2021

Cited by 6 | Viewed by 2256

Abstract

Background: The purpose of the present study was to longitudinally characterize the supragingival microbiota throughout a three months period in orally healthy individuals. We tested the hypothesis that the supragingival microbiota shows a high degree of compositional stability, which is resilient against the [...] Read more.

Background: The purpose of the present study was to longitudinally characterize the supragingival microbiota throughout a three months period in orally healthy individuals. We tested the hypothesis that the supragingival microbiota shows a high degree of compositional stability, which is resilient against the external perturbation of regular use of probiotics, as long as oral health is maintained. Methods: The present study was a double-blinded, randomized, placebo-controlled clinical trial. The study population comprised a total of 110 oral and systemic healthy individuals, distributed in a probiotic (n = 55) and placebo (n = 55) group, where the test group consumed tablets with the probiotic strains Lacticaseibacillusrhamnosus (formerly Lactobacillus) PB01 DSM14870 and Latilactobacillus curvatus (formerly Lactobacillus) EB10 DSM32307 for a period of 12 weeks. Supragingival plaque samples and clinical registrations were performed at baseline, and after 4, 8, and 12 weeks, respectively. The supragingival microbiota was characterized by means of 16S rDNA sequencing. Sequences were referenced against the HOMD database. Results: No significant changes of the core microbiota, as expressed by relative abundance of predominant genera and species were evident during the three months observation period in the probiotic or the placebo group. Conclusions: Data from the present study clearly demonstrate long term compositional stability of the supragingival microbiota as long as oral health is maintained. In addition, the tested probiotics had no augmenting effect on the supragingival microbiota in oral health. Full article

(This article belongs to the Special Issue Oral Immunology and Periodontitis)

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14 pages, 2407 KiB

Open AccessArticle

Activation of Gingival Fibroblasts by Bacterial Cyclic Dinucleotides and Lipopolysaccharide

by Samira Elmanfi, Herman O. Sintim, Jie Zhou, Mervi Gürsoy, Eija Könönen and Ulvi K. Gürsoy

Pathogens 2020, 9(10), 792; https://doi.org/10.3390/pathogens9100792 - 26 Sep 2020

Cited by 10 | Viewed by 3130

Abstract

Human gingival fibroblasts (HGFs) recognize microbe-associated molecular patterns (MAMPs) and respond with inflammatory proteins. Simultaneous impacts of bacterial cyclic di-guanosine monophosphate (c-di-GMP), cyclic di-adenosine monophosphate (c-di-AMP), and lipopolysaccharide (LPS) on gingival keratinocytes have been previously demonstrated, but the effects of these MAMPs on [...] Read more.

Human gingival fibroblasts (HGFs) recognize microbe-associated molecular patterns (MAMPs) and respond with inflammatory proteins. Simultaneous impacts of bacterial cyclic di-guanosine monophosphate (c-di-GMP), cyclic di-adenosine monophosphate (c-di-AMP), and lipopolysaccharide (LPS) on gingival keratinocytes have been previously demonstrated, but the effects of these MAMPs on other periodontal cell types, such as gingival fibroblasts, remain to be clarified. The present aim was to examine the independent and combined effects of these cyclic dinucleotides and LPS on interleukin (IL) and matrix metalloproteinase (MMP) response of HGFs. The cells were incubated with c-di-GMP and c-di-AMP, either in the presence or absence of Porphyromonas gingivalis LPS, for 2 h and 24 h. The levels of IL-8, -10, and -34, and MMP-1, -2, and -3 secreted were measured by the Luminex technique. LPS alone or together with cyclic dinucleotides elevated IL-8 levels. IL-10 levels were significantly increased in the presence of c-di-GMP and LPS after 2 h but disappeared after 24 h of incubation. Concurrent treatment of c-di-AMP and LPS elevated MMP-1 levels, whereas c-di-GMP with LPS suppressed MMP-2 levels but increased MMP-3 levels. To conclude, we produce evidence that cyclic dinucleotides interact with LPS-mediated early response of gingival fibroblasts, while late cellular response is mainly regulated by LPS. Full article

(This article belongs to the Special Issue Oral Immunology and Periodontitis)

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11 pages, 6043 KiB

Open AccessEditor’s ChoiceArticle

Elevated Baseline Salivary Protease Activity May Predict the Steadiness of Gingival Inflammation During Periodontal Healing: A 12-Week Follow-Up Study on Adults

by Ulvi Kahraman Gürsoy, Dareen Fteita, Floris J. Bikker, Maria Anastasia Grande, Kamran Nazmi, Mervi Gürsoy, Eija Könönen and Daniel Belstrøm

Pathogens 2020, 9(9), 751; https://doi.org/10.3390/pathogens9090751 - 15 Sep 2020

Cited by 8 | Viewed by 2708

Abstract

Aim was to profile salivary total protease, Porphyromonas gingivalis gingipain, and neutrophil elastase activities in relation to the resolution of periodontal inflammation, salivary macrophage-derived chemokine (MDC), and macrophage inflammatory protein-1α concentrations. Nonsurgical periodontal treatment was performed in 24 periodontitis patients in a prospective [...] Read more.

Aim was to profile salivary total protease, Porphyromonas gingivalis gingipain, and neutrophil elastase activities in relation to the resolution of periodontal inflammation, salivary macrophage-derived chemokine (MDC), and macrophage inflammatory protein-1α concentrations. Nonsurgical periodontal treatment was performed in 24 periodontitis patients in a prospective interventional study design. Periodontal clinical parameters were recorded, and stimulated saliva samples were collected at baseline and 2, 6, and 12 weeks after treatment. Salivary total protease and gingipain activities were determined using fluorogenic substrates, elastase activity by chromogenic substrates, and cytokine concentrations by Luminex immunoassay. For statistical analyses, generalized linear mixed models for repeated measures were used. Salivary total protease activity elevated, while gingival inflammation and plaque accumulation decreased 2 and 6 weeks after periodontal therapy. Salivary MDC concentration was elevated 12 weeks after periodontal treatment. Patients with elevated protease activities at baseline in comparison to patients with low baseline total protease activities, had higher levels of gingival inflammation before and after periodontal treatment. In conclusion, elevations in salivary total protease activity seem to be part of periodontal healing at its early phases. Higher levels of salivary total protease activities before periodontal treatment may predict the severity and steadiness of unresolved gingival inflammation. Full article

(This article belongs to the Special Issue Oral Immunology and Periodontitis)

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14 pages, 1999 KiB

Open AccessArticle

43-Year Temporal Trends in Immune Response to Oral Bacteria in a Swedish Population

by Anders Esberg, Anders Johansson, Rolf Claesson and Ingegerd Johansson

Pathogens 2020, 9(7), 544; https://doi.org/10.3390/pathogens9070544 - 7 Jul 2020

Cited by 7 | Viewed by 2080

Abstract

Bacteria colonizing the mouth induce an adaptive immune response with the systemic and local presence of species or strain-specific immunoglobulins. Few studies have addressed global antibody patterns for oral bacteria or potential population time trends. We assessed these aspects in relation to a [...] Read more.

Bacteria colonizing the mouth induce an adaptive immune response with the systemic and local presence of species or strain-specific immunoglobulins. Few studies have addressed global antibody patterns for oral bacteria or potential population time trends. We assessed these aspects in relation to a panel of oral bacteria. Using multiplex immunoblotting, IgG levels for 26 oral bacterial species (54 strains) were determined in 888 plasma samples from 30-year-old early pregnant women (n = 516) and 50-year-old men and women (n = 372) collected between 1976 and 2018. Inter-species correlations were found and age-dependent profiles and levels of immune responses to oral bacteria confirmed. We found temporal trends in the global and single-species antibody responses, but this was age-specific with both inclining and declining shifts. Prominent shifts in the younger group increased IgG towards health-associated Streptococcus salivarius and Streptococcus sanguinis, and in the older group towards disease-associated Aggregatibacter actinomycetemcomitans, Filifactor alocis, and Streptococcus mutans, among others. We concluded that temporal shifts occurred from 1976 to 2018, which may reflect improved oral health (more remaining teeth) and altered lifestyle habits, but this needs to be evaluated in observational studies considering more aspects. Full article

(This article belongs to the Special Issue Oral Immunology and Periodontitis)

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Review

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18 pages, 891 KiB

Open AccessReview

Vascular Changes and Hypoxia in Periodontal Disease as a Link to Systemic Complications

by Dilek Celik and Alpdogan Kantarci

Pathogens 2021, 10(10), 1280; https://doi.org/10.3390/pathogens10101280 - 5 Oct 2021

Cited by 23 | Viewed by 5108

Abstract

The hypoxic microenvironment caused by oral pathogens is the most important cause of the disruption of dynamic hemostasis between the oral microbiome and the immune system. Periodontal infection exacerbates the inflammatory response with increased hypoxia and causes vascular changes. The chronicity of inflammation [...] Read more.

The hypoxic microenvironment caused by oral pathogens is the most important cause of the disruption of dynamic hemostasis between the oral microbiome and the immune system. Periodontal infection exacerbates the inflammatory response with increased hypoxia and causes vascular changes. The chronicity of inflammation becomes systemic as a link between oral and systemic diseases. The vascular network plays a central role in controlling infection and regulating the immune response. In this review, we focus on the local and systemic vascular network change mechanisms of periodontal inflammation and the pathological processes of inflammatory diseases. Understanding how the vascular network influences the pathology of periodontal diseases and the systemic complication associated with this pathology is essential for the discovery of both local and systemic proactive control mechanisms. Full article

(This article belongs to the Special Issue Oral Immunology and Periodontitis)

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6 pages, 573 KiB

Open AccessReview

Pyruvate Kinase, Inflammation and Periodontal Disease

by Melissa M. Grant

Pathogens 2021, 10(7), 784; https://doi.org/10.3390/pathogens10070784 - 22 Jun 2021

Cited by 8 | Viewed by 4305

Abstract

Pyruvate kinase (PK) is the final and rate-limiting enzyme in glycolysis. It has four isoforms PKM1, PKM2, PKL and PKR. PK can form homo tetramers, dimers or monomers. The tetrameric form has the most catalytic activity; however, the dimeric form has non-canonical functions [...] Read more.

Pyruvate kinase (PK) is the final and rate-limiting enzyme in glycolysis. It has four isoforms PKM1, PKM2, PKL and PKR. PK can form homo tetramers, dimers or monomers. The tetrameric form has the most catalytic activity; however, the dimeric form has non-canonical functions that contribute to the inflammatory response, wound healing and cellular crosstalk. This brief review explores these functions and speculates on their role in periodontal disease. Full article

(This article belongs to the Special Issue Oral Immunology and Periodontitis)

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12 pages, 6049 KiB

Open AccessReview

Bacterial Cyclic Dinucleotides and the cGAS–cGAMP–STING Pathway: A Role in Periodontitis?

by Samira Elmanfi, Mustafa Yilmaz, Wilson W. S. Ong, Kofi S. Yeboah, Herman O. Sintim, Mervi Gürsoy, Eija Könönen and Ulvi K. Gürsoy

Pathogens 2021, 10(6), 675; https://doi.org/10.3390/pathogens10060675 - 30 May 2021

Cited by 13 | Viewed by 4871

Abstract

Host cells can recognize cytosolic double-stranded DNAs and endogenous second messengers as cyclic dinucleotides—including c-di-GMP, c-di-AMP, and cGAMP—of invading microbes via the critical and essential innate immune signaling adaptor molecule known as STING. This recognition activates the innate immune system and leads to [...] Read more.

Host cells can recognize cytosolic double-stranded DNAs and endogenous second messengers as cyclic dinucleotides—including c-di-GMP, c-di-AMP, and cGAMP—of invading microbes via the critical and essential innate immune signaling adaptor molecule known as STING. This recognition activates the innate immune system and leads to the production of Type I interferons and proinflammatory cytokines. In this review, we (1) focus on the possible role of bacterial cyclic dinucleotides and the STING/TBK1/IRF3 pathway in the pathogenesis of periodontal disease and the regulation of periodontal immune response, and (2) review and discuss activators and inhibitors of the STING pathway as immune response regulators and their potential utility in the treatment of periodontitis. PubMed/Medline, Scopus, and Web of Science were searched with the terms “STING”, “TBK 1”, “IRF3”, and “cGAS”—alone, or together with “periodontitis”. Current studies produced evidence for using STING-pathway-targeting molecules as part of anticancer therapy, and as vaccine adjuvants against microbial infections; however, the role of the STING/TBK1/IRF3 pathway in periodontal disease pathogenesis is still undiscovered. Understanding the stimulation of the innate immune response by cyclic dinucleotides opens a new approach to host modulation therapies in periodontology. Full article

(This article belongs to the Special Issue Oral Immunology and Periodontitis)

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23 pages, 1956 KiB

Open AccessEditor’s ChoiceReview

Porphyromonas gingivalis and Its Systemic Impact: Current Status

by Feng Mei, Mengru Xie, Xiaofei Huang, Yanlin Long, Xiaofeng Lu, Xiaoli Wang and Lili Chen

Pathogens 2020, 9(11), 944; https://doi.org/10.3390/pathogens9110944 - 13 Nov 2020

Cited by 91 | Viewed by 11135

Abstract

The relationship between periodontitis and systemic diseases, notably including atherosclerosis and diabetes, has been studied for several years. Porphyromonas gingivalis, a prominent component of oral microorganism communities, is the main pathogen that causes periodontitis. As a result of the extensive analysis of [...] Read more.

The relationship between periodontitis and systemic diseases, notably including atherosclerosis and diabetes, has been studied for several years. Porphyromonas gingivalis, a prominent component of oral microorganism communities, is the main pathogen that causes periodontitis. As a result of the extensive analysis of this organism, the evidence of its connection to systemic diseases has become more apparent over the last decade. A significant amount of research has explored the role of Porphyromonas gingivalis in atherosclerosis, Alzheimer’s disease, rheumatoid arthritis, diabetes, and adverse pregnancy outcomes, while relatively few studies have examined its contribution to respiratory diseases, nonalcoholic fatty liver disease, and depression. Here, we provide an overview of the current state of knowledge about Porphyromonas gingivalis and its systemic impact in an aim to inform readers of the existing epidemiological evidence and the most recent preclinical studies. Additionally, the possible mechanisms by which Porphyromonas gingivalis is involved in the onset or exacerbation of diseases, together with its effects on systemic health, are covered. Although a few results remain controversial, it is now evident that Porphyromonas gingivalis should be regarded as a modifiable factor for several diseases. Full article

(This article belongs to the Special Issue Oral Immunology and Periodontitis)

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