Application of intentional replantation in advanced periodontitis involving teeth preservation.

With the development of periodontal regenerative technology, an increasing number of scholars reported that advanced periodontitis involving teeth can be preserved through intentional replantation. Intentional replantation has become the last possible method to preserve natural teeth for advance periodontitis with signs of tooth extraction. However, the indications of intentional replantation are strict, and the success of the operation is closely related to the condition of cases and the operation skills of doctors. In this article, the operation steps and criteria of intentional replantation were summarized by introducing three success cases of advanced periodontitis involving teeth preserved by intentional replantation. The relevant factors that affect the prognosis of intentional replantation in advanced periodontitis involving teeth preservation were analyzed to help clinicians preserve natural teeth.

Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis.

Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice. In the context of disease, nisin treatment significantly shifted the microbiome towards a new composition, commensurate with health while preventing the harmful inflammation in the small intestine concomitant with decreased villi structural integrity, and heightened hepatic exposure to bacteria and lipid and malondialdehyde accumulation in the liver. Validation with RNA Seq analyses, confirmed the significant infection-related alteration of several genes involved in mitochondrial dysregulation, oxidative phosphorylation, and metal/iron binding and their restitution following nisin treatment. In support of these in vivo findings indicating that periodontopathogens induce gastrointestinal and liver distant organ lesions, human autopsy specimens demonstrated a correlation between tooth loss and severity of liver disease. Nisin's ability to shift the gut and liver microbiome towards a new state commensurate with health while mitigating enteritis, represents a novel approach to treating NAFLD-steatohepatitis-associated periodontal disease.

Nisin a probiotic bacteriocin mitigates brain microbiome dysbiosis and Alzheimer's disease-like neuroinflammation triggered by periodontal disease.

INTRODUCTION: Periodontitis-related oral microbial dysbiosis is thought to contribute to Alzheimer's disease (AD) neuroinflammation and brain amyloid production. Since probiotics can modulate periodontitis/oral dysbiosis, this study examined the effects of a probiotic/lantibiotic, nisin, in modulating brain pathology triggered by periodontitis. METHODS: A polymicrobial mouse model of periodontal disease was used to evaluate the effects of this disease on brain microbiome dysbiosis, neuroinflammation, Alzheimer's-related changes, and nisin's therapeutic potential in this context. RESULTS: 16S sequencing and real-time PCR data revealed that Nisin treatment mitigated the changes in the brain microbiome composition, diversity, and community structure, and reduced the levels of periodontal pathogen DNA in the brain induced by periodontal disease. Nisin treatment significantly decreased the mRNA expression of pro-inflammatory cytokines (Interleukin-1ß/IL-1 ß, Interleukin 6/IL-6, and Tumor Necrosis Factor α/TNF-α) in the brain that were elevated by periodontal infection. In addition, the concentrations of amyloid-ß 42 (Aß42), total Tau, and Tau (pS199) (445.69 ± 120.03, 1420.85 ± 331.40, 137.20 ± 36.01) were significantly higher in the infection group compared to the control group (193.01 ± 31.82, 384.27 ± 363.93, 6.09 ± 10.85), respectively. Nisin treatment markedly reduced the Aß42 (261.80 ± 52.50), total Tau (865.37 ± 304.93), and phosphorylated Tau (82.53 ± 15.77) deposition in the brain of the infection group. DISCUSSION: Nisin abrogation of brain microbiome dysbiosis induces beneficial effects on AD-like pathogenic changes and neuroinflammation, and thereby may serve as a potential therapeutic for periodontal-dysbiosis-related AD.

Nisin probiotic prevents inflammatory bone loss while promoting reparative proliferation and a healthy microbiome.

Dysbiosis of the oral microbiome mediates chronic periodontal disease. Realignment of microbial dysbiosis towards health may prevent disease. Treatment with antibiotics and probiotics can modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. Antibacterial peptides or bacteriocins, such as nisin, and a nisin-producing probiotic, Lactococcus lactis, have not been examined in this context, yet warrant examination because of their biomedical benefits in eradicating biofilms and pathogenic bacteria, modulating immune mechanisms, and their safety profile in humans. This study's goal was to examine the potential for nisin and a nisin-producing probiotic to abrogate periodontal bone loss, the host inflammatory response, and changes in oral microbiome composition in a polymicrobial mouse model of periodontal disease. Nisin and a nisin-producing Lactococcus lactis probiotic significantly decreased the levels of several periodontal pathogens, alveolar bone loss, and the oral and systemic inflammatory host response. Surprisingly, nisin and/or the nisin-producing L. lactis probiotic enhanced the population of fibroblasts and osteoblasts despite the polymicrobial infection. Nisin mediated human periodontal ligament cell proliferation dose-dependently by increasing the proliferation marker, Ki-67. Nisin and probiotic treatment significantly shifted the oral microbiome towards the healthy control state; health was associated with Proteobacteria, whereas 3 retroviruses were associated with disease. Disease-associated microbial species were correlated with IL-6 levels. Nisin or nisin-producing probiotic's ability to shift the oral microbiome towards health, mitigate periodontal destruction and the host immune response, and promote a novel proliferative phenotype in reparative connective tissue cells, addresses key aspects of the pathogenesis of periodontal disease and reveals a new biomedical application for nisin in treatment of periodontitis and reparative medicine.

Clinical study showing a lower abundance of Neisseria in the oral microbiome aligns with low birth weight pregnancy outcomes.

OBJECTIVES: The objective of this study was to examine the association between the oral microbiome and pregnancy outcomes, specifically healthy or preterm low birth weight (PLBW) in individuals with and without periodontal disease (PD). MATERIAL AND METHODS: In this prospective clinical trial, we recruited 186 pregnant women, 17 of whom exhibited PD and delivered PLBW infants (PD-PLBW group). Of the remaining women, 155 presented PD and delivered healthy infants; 18 of these subjects with similar periodontal condition and age matched to the PD-PLBW group, and they became the PD-HD group. From the total group, 11 women exhibited healthy gingiva and had a healthy delivery (HD) and healthy infants (H-HD group), and 3 exhibited healthy gingiva and delivered PLBW infants (H-PLBW group). Periodontal parameters were recorded, and subgingival plaque and serum were collected during 26-28 gestational weeks. For the plaque samples, microbial abundance and diversity were accessed by 16S rRNA sequencing. RESULTS: Women with PD showed an enrichment in the genus Porphyromonas, Treponema, and Filifactor, whereas women with healthy gingiva showed an enrichment in Streptococcus, Actinomyces, and Corynebacterium, independently of the birth status. Although no significant difference was found in the beta diversity between the 4 groups, women that had PLBW infants presented a significantly lower abundance of the genus Neisseria, independently of PD status. CONCLUSION: Lower levels of Neisseria align with preterm low birth weight in pregnant women, whereas a higher abundance of Treponema, Porphyromonas, Fretibacterium, and Filifactor and a lower abundance of Streptococcus may contribute to periodontal disease during pregnancy. CLINICAL RELEVANCE: The oral commensal Neisseria have potential in the prediction of PLBW.

Diagnostic potential and future directions of matrix metalloproteinases as biomarkers in gingival crevicular fluid of oral and systemic diseases.

Gingival crevicular fluid (GCF) is a physiological fluid and an inflammatory serum exudate derived from the gingival plexus of blood vessels and mixed with host tissues and subgingival plaque flows. In addition to proteins, GCF contains a diverse population of cells, including desquamated epithelial cells, cytokines, electrolytes, and bacteria from adjacent plaques. Recently, matrix metalloproteinases(MMPs), which are endopeptidases that are active against extracellular macromolecules, in GCF have been revealed as potential utility biomarkers for the diagnosis and follow-up of oral and systemic diseases, thereby facilitating the early evaluation of malignancy risk and the monitoring of disease progression and treatment response. Tissue inhibitors of metalloproteinases (TIMPs) are specific inhibitors of matrixins that participate in the regulation of local activities of MMPs in tissues. This review provides an overview of the latest findings on the diagnostic and prognostic values of MMPs and TIMPs in GCF of oral and systemic diseases, including periodontal disease, pulpitis, peri-implantitis and cardiovascular disease as well as the extraction, detection and analytical methods for GCF.

Oral microbiome shifts during pregnancy and adverse pregnancy outcomes: Hormonal and Immunologic changes at play.

Because of hormonal and immunologic changes, there are significant changes in the oral microbiome that emerge during pregnancy. Recent evidence further suggests that there is an association between the presence of periodontal disease and a pregnancy-associated oral dysbiosis. Although this oral dysbiosis and pathogenic periodontal bacteria are considered to be associated with adverse pregnancy outcomes, it is still not clear how an oral dysbiosis during pregnancy can modulate oral diseases and birth outcomes. To develop preventive or therapeutic interventions, it is critical to understand the oral microbiome changes that emerge during pregnancy and their association with adverse pregnancy outcomes. In the present review, we summarize the current literature on normal changes in the oral microbiome that occur during pregnancy; the pathogenic changes in the oral microbiome believed to occur in association with adverse pregnancy outcomes; and the association between the placental microbiome and the oral microbiome.

[Treatment strategy for pregnancy epulis].

Pregnancy epulis is a tumor-like lesion with high prevalence in China. The local lesion, the general condition of the pregnant patient, and the complications during treatment should be taken into consideration when making a treatment plan for pregnancy epulis. In this study, three representative pregnancy epulis cases were presented, and related studies at home and aboard were reviewed to summarize the etiology, differential diagnosis, treatment, and prevention of pregnancy epulis and share the clinical experience in the treatment of pregnancy epulis.

Modulation of pathogenic oral biofilms towards health with nisin probiotic.

BACKGROUND: Oral dysbiosis is an imbalance in the oral microbiome and is associated with a variety of oral and systemic diseases, including periodontal disease, caries, and head and neck/oral cancer. Although antibiotics can be used to control this dysbiosis, they can lead to adverse side effects and superinfections. Thus, novel strategies have been proposed to address these shortcomings. One strategy is the use of probiotics as antimicrobial agents, since they are considered safe for humans and the environment. Specifically, the Gram-positive Lactococcus lactis, a species present in the oral and gut microbiota, is able to produce nisin, which has been used worldwide for food preservation. OBJECTIVE: The objective of this study was to test whether a nisin probiotic can promote a healthier oral microbiome in pathogen-spiked oral biofilms. RESULTS: We found that L. lactis can prevent oral biofilm formation and disrupt 24-h and 48-h pre-formed biofilms. Finally, we demonstrate that both treatments, a nisin-producing L. lactis probiotic and nisin can decrease the levels of pathogens in the biofilms and return the diversity levels back to control or 'healthy' levels. CONCLUSION: A nisin-producing probiotic, can be used to treat 'disease-altered' biofilms and promote healthier oral biofilms, which may be useful for improving patient oral health.

Unculturable and culturable periodontal-related bacteria are associated with periodontal inflammation during pregnancy and with preterm low birth weight delivery.

Recent studies revealed culturable periodontal keystone pathogens are associated with preterm low birth weight (PLBW). However, the oral microbiome is also comprised of hundreds of 'culture-difficult' or 'not-yet-culturable' bacterial species. To explore the potential role of unculturable and culturable periodontitis-related bacteria in preterm low birth weight (PLBW) delivery, we recruited 90 pregnant women in this prospective study. Periodontal parameters, including pocket probing depth, bleeding on probing, and clinical attachment level were recorded during the second trimester and following interviews on oral hygiene and lifestyle habits. Saliva and serum samples were also collected. After delivery, birth results were recorded. Real-time PCR analyses were performed to quantify the levels of periodontitis-related unculturable bacteria (Eubacterium saphenum, Fretibacterium sp. human oral taxon(HOT) 360, TM7 sp. HOT 356, and Rothia dentocariosa), and cultivable bacteria (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum and Prevotella intermedia) in saliva samples. In addition, ELISA analyses were used to determine the IgG titres against periodontal pathogens in serum samples. Subjects were categorized into a Healthy group (H, n = 20) and periodontitis/gingivitis group (PG, n = 70) according to their periodontal status. The brushing duration was significantly lower in the PG group compared to the H group. Twenty-two of 90 subjects delivered PLBW infants. There was no significant difference in periodontal parameters and serum IgG levels for periodontal pathogens between PLBW and healthy delivery (HD) groups. However, ordinal logistic regression analysis revealed that a higher abundance of Treponema denticola, Prevotella intermedia, Fretibacterium sp. HOT360 and lower levels of Rothia dentocariosa were significantly associated with the presence of periodontal disease during pregnancy. Moreover, the amount of Eubacterium saphenum in saliva and serum IgG against Aggregatibacter actinomycetemcomitans were negatively correlated with PLBW. Taken together, unculturable periodontitis-associated bacteria may play an important role both in the presence of periodontal inflammation during pregnancy and subsequent PLBW.

The periodontopathic bacteria in placenta, saliva and subgingival plaque of threatened preterm labor and preterm low birth weight cases: a longitudinal study in Japanese pregnant women.

OBJECTIVES: This study determined the quantity of periodontopathic bacteria in saliva, subgingival plaque, and placenta on the threatened preterm labor (TPL) and preterm low birth weight (PLBW) subjects in order to identify specific periodontal pathogens with high association to adverse pregnancy outcomes. METHODS: We used real-time PCR with TaqMan probe and ELISA to detect the amount of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum, and Prevotella intermedia in subgingival plaque, saliva, and placenta tissue, in addition to serum IgG titers against these bacteria in 28 patients with TPL and 36 healthy pregnant women. RESULTS: Thirteen of 64 births delivered PLBW infants. All 6 periodontopathic bacteria were detected in the placenta samples. The amount of F. nucleatum and detection frequency of T. denticola in placental samples was significantly higher in the TPL group than in the healthy group. Meanwhile, the age, anti-P. gingival IgG in serum, amount of P. gingivalis and T. forsythia in plaque samples, detection frequency of P. intermedia in saliva, and percentage of pocket probing depth ≥ 5 mm were higher in TPL-PLBW births than those in TPL-Healthy delivery (HD) group and/or in H-HD group. Ordinal logistic regression analysis revealed that the presence of F. nucleatum in placental tissues was significantly associated with TPL, while the maternal age was significantly associated with PLBW in TPL. CONCLUSION: Our findings suggested all 6 bacteria may access the placenta. The increased presence of F. nucleatum in placenta might be related to TPL, while advanced maternal age might be associated with PLBW in TPL. CLINICAL RELEVANCE: Periodontal therapy should be applied to reduce the deep periodontal pocket sites and the colonization of periodontal pathogens in high-risk population.

The relationship between the anti-Porphyromonas gingivalis immunoglobulin G subclass antibody and small for gestational age delivery: a longitudinal study in pregnant Japanese women.

BACKGROUND: Maternal serum IgG antibody against Porphyromonas gingivalis is an indicator of both periodontitis and adverse pregnancy outcomes. This study aims to evaluate the anti-P. gingivalis IgG and IgG subclasses1-4 in threatened preterm labour (TPL) patients and their association with small for gestational age (SGA). METHODS: Serum, saliva and subgingival plaque samples were collected from 47 TPL patients compared with 48 healthy pregnant women. The amount of P. gingivalis was measured in saliva and plaque using real-time polymerase chain reaction. The serum anti-P. gingivalis IgG titre and anti-P. gingivalis subclasses IgG 1-4 concentration were measured using enzyme-linked immunosorbent assay. RESULTS: The amount of anti-P. gingivalis IgG-1 was significantly lower in the TPL group than in the healthy group. Fourteen subjects delivered SGA infants in the TPL group. The pocket probing depth (PPD), clinical attachment loss, PPD ≥ 5 mm%, amount of P. gingivalis in plaque, anti-P. gingivalis IgG and anti-P. gingivalis IgG-4 were significantly higher in the TPL-SGA group than in the TPL-normal weight group. Moreover, logistic regression analysis revealed the detection frequency of P. gingivalis in plaque and placenta weight were significantly correlated with SGA in TPL. In the receiver operating characteristic curve analysis, an amount of P. gingivalis in plaque ≥ 86.45 copies showed a sensitivity of 0.786 and a specificity of 0.727 (AUC 0.792) for predicting SGA in TPL. CONCLUSION: Lower anti-P. gingivalis IgG-1 amounts are related to TPL, while higher anti-P. gingivalis IgG and IgG-4 are related with SGA in TPL. Further, greater colonisation of P. gingivalis in plaque might increase the risk of SGA and can be useful in prediction of SGA in TPL.

Polymicrobial periodontal disease triggers a wide radius of effect and unique virome.

Periodontal disease is a microbially-mediated inflammatory disease of tooth-supporting tissues that leads to bone and tissue loss around teeth. Although bacterially-mediated mechanisms of alveolar bone destruction have been widely studied, the effects of a polymicrobial infection on the periodontal ligament and microbiome/virome have not been well explored. Therefore, the current investigation introduced a new mouse model of periodontal disease to examine the effects of a polymicrobial infection on periodontal ligament (PDL) properties, changes in bone loss, the host immune response, and the microbiome/virome using shotgun sequencing. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Fusobacterium nucleatum were used as the polymicrobial oral inoculum in BALB/cByJ mice. The polymicrobial infection triggered significant alveolar bone loss, a heightened antibody response, an elevated cytokine immune response, a significant shift in viral diversity and virome composition, and a widening of the PDL space; the latter two findings have not been previously reported in periodontal disease models. Changes in the PDL space were present at sites far away from the site of insult, indicating that the polymicrobial radius of effect extends beyond the bone loss areas and site of initial infection and wider than previously appreciated. Associations were found between bone loss, specific viral and bacterial species, immune genes, and PDL space changes. These findings may have significant implications for the pathogenesis of periodontal disease and biomechanical properties of the periodontium. This new polymicrobial mouse model of periodontal disease in a common mouse strain is useful for evaluating the features of periodontal disease.

Probiotics, including nisin-based probiotics, improve clinical and microbial outcomes relevant to oral and systemic diseases.

The effects of probiotic supplementation on systemic health and gastrointestinal diseases have been investigated in numerous studies. The aim of this review is to provide an overview of probiotics and their effects on periodontal health. Probiotics show beneficial effects as adjunctive therapeutics and as stand-alone agents in the treatment and prevention of gingivitis as well as specific clinical parameters of periodontitis. This review focuses on the clinical and microbiological aspects of probiotics in the context of health, gingivitis, and periodontitis. In addition, a special focus on nisin-producing probiotics and nisin itself showcase their significant potential for oral and systemic use.

EB 2017 Article: Changes in advanced glycation end products, beta-defensin-3, and interleukin-17 during diabetic periodontitis development in rhesus monkeys.

The bidirectional relationship between diabetes mellitus (DM) and periodontal disease has drawn great attention; however, the mechanisms underlying their association remain unclear. In this study, we aimed to develop a rhesus monkey model of diabetic periodontitis and explore the potential mechanisms by which DM affects the progression of periodontal disease. Three healthy rhesus monkeys were selected as the control group. Five streptozotocin-induced diabetic rhesus monkeys were chosen as the experimental group. Ligature placement was used to induce periodontitis. The changes in the levels of advanced glycation end products (AGEs), beta-defensin-3 (BD-3), and interleukin-17 (IL-17) were measured using enzyme-linked immunosorbent assays (ELISA) and real-time reverse transcription polymerase chain reaction (RT-PCR) at different stages during disease progression. Periodontitis was confirmed by clinical assessment, radiographic images, and histological examination. Significant changes in the levels of AGEs and BD-3 in serum were observed at the periodontitis stage in diabetic rhesus monkeys ( P < 0.05). The expression of BD-3 mRNA in the gingiva of diabetic group at baseline was significantly high ( P < 0.05). Diabetic monkeys exhibited significantly enhanced IL-17 mRNA expression at the periodontitis stage ( P < 0.05). Our findings indicated that the rhesus monkey can serve as an ideal model for exploring the pathogenesis of diabetic periodontitis, and the hyperglycemic environment may accelerate inflammatory response and weaken the defense system in periodontal tissues. Impact statement The mechanism underlying the association between diabetes mellitus (DM) and periodontal disease is not yet fully understood. Hence, there is a need to establish animal models to reveal the effect of DM on the pathogenesis of periodontitis. In this study, we explored the appropriate methods for inducing periodontitis and shortening the modeling time in rhesus monkeys, to investigate the pathogenesis of diabetic periodontitis and develop innovative therapies. Our results suggest that a hyperglycemic environment might lead to the destruction of periodontal tissues by accelerating inflammatory response and weakening the defense system in periodontal tissues. Therefore, this study has significant treatment implications regarding the regulation of the immune response against periodontal diseases in patients with DM.

The anti-phospholipid antibody-dependent and independent effects of periodontopathic bacteria on threatened preterm labor and preterm birth.

PURPOSE: Periodontal disease is considered to be a risk factor for threatened preterm labor (TPL) and preterm birth (PB), but pathogenic mechanisms have not yet been elucidated. We hypothesized that infection with periodontopathic bacteria may enhance thrombosis through molecular mimicry with TLRVYK peptides on beta-2 glycoprotein I, a target molecule in anti-phospholipid syndrome. This study aimed to examine the effects of periodontitis on TPL and PB. METHODS: Ninety-five pregnant women (47 TPL and 48 healthy subjects) participated. Periodontal clinical parameters and periodontopathic bacteria were examined. Molecular mimicry between TLRVYK peptides and homologous peptides on the periodontopathic bacteria was examined by enzyme-linked immunosorbent assay (ELISA) using rabbit polyclonal antibodies specific for the respective peptides (SIRVYK on Aggregatibacter actinomycetemcomitans, TLRIYT on Porphyromonus gingivalis, and TLALYK on Treponema denticola). Serum high-sensitivity C-reactive protein, anti-TLRVYK and anti-SIRVYK IgG antibodies were measured using ELISA. RESULTS: Among the rabbit antibodies specific for the bacterial homologous peptides, only anti-SIRVYK IgG antibody reacted with TLRVYK peptides. Multivariable analysis showed that anti-SIRVYK IgG antibody was significantly associated with diagnosis of TPL. Of 95 births, 14 (14.7 %) delivered preterm. The preterm birth rate was higher in the anti-SIRVYK IgG antibody >median group than in the ≤median group. Of the 47 TPL subjects 13 had PB, and ordinal logistic regression analysis revealed that past smoking, presence of P. gingivalis and anti-SIRVYK IgG antibody were significantly correlated with PB. CONCLUSIONS: Infection with P. gingivalis and the antibody response to SIRVYK might be associated with TPL and PB.

[Squamous cell papilloma in interdental papilla: a case report].

Squamous cell papilloma is a kind of benign tumor from mucosa stratified squamous epithelium, which usually occurs in cheek, palate, lip and tongue. In this paper, a case of squamous cell papilloma occurred in interdental papilla was reported, and its pathogenesis, clinic features and treatment were discussed.