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.

The Last Molar - Entire Pad Preservation Technique (L-EPPT) as a Regenerative Surgical Approach for Combined Distal Intrabony Defects and Furcation Involvement: Case Reports.

Primary wound closure is the most important factor in successful periodontal tissue regeneration when using biomaterials. However, in the distal region of the last molar, there is concern that direct surgical access to an intraosseous defect may induce the leakage of biomaterials, impair the blood supply, and make healing difficult. This case series introduces the last molar-entire pad preservation technique (L-EPPT), which was designed to preserve the gingiva of the last molar centrum and secure the operative field of the furcation and distal bone defects, thereby providing an optimal environment for wound healing for regenerative therapy. This technique for preservation of the distal gingiva was applied in two cases involving the combination of a buccal class II furcation defect and a 2-3-wall intrabony defect in the last molar for the use of a combination of bone graft and enamel matrix derivatives in periodontal regeneration. Clinical outcomes were recorded at 18 months (case 1) and 8 months (case 2) after surgery. In both cases, the class II furcation defects were completely closed, and the probing pocket depth was improved to < 3 mm with no bleeding on probing. Further research is warranted to verify the efficacy of this technique.

Biomaterials for Alveolar Ridge Preservation as a Preoperative Procedure for Implant Treatment: History and Current Evidence.

In implant treatment, the reduction and structural changes in the alveolar ridge that occur after tooth extraction limit the length, width, and placement position of the implant body, impair esthetics, and, in some cases, make implant placement difficult. To solve these problems, an alveolar ridge preservation (ARP) technique, which is performed simultaneously with tooth extraction, generally aims to promote bone regeneration and prevent alveolar ridge reduction by filling the extraction socket with bone graft material and then covering it with a barrier membrane to protect against the invasion of epithelial tissue. The extraction socket provides a favorable environment for bone regeneration throughout the healing period because the blood supply is abundant, and it effectively retains the bone graft material by using the remaining bone wall of the socket. In recent years, advances in bioengineering technology have led to the development of graft materials with various biological properties, but there is currently no clear consensus regarding the selection of surgical techniques and materials depending on the condition of the alveolar ridge. This review will provide a comprehensive survey of the evidence accumulated to date on ARP, present many cases according to the clinical situation, and discuss various treatment options.

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.

Periodontal treatment and microbiome-targeted therapy in management of periodontitis-related nonalcoholic fatty liver disease with oral and gut dysbiosis.

A growing body of evidence from multiple areas proposes that periodontal disease, accompanied by oral inflammation and pathological changes in the microbiome, induces gut dysbiosis and is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). A subgroup of NAFLD patients have a severely progressive form, namely nonalcoholic steatohepatitis (NASH), which is characterized by histological findings that include inflammatory cell infiltration and fibrosis. NASH has a high risk of further progression to cirrhosis and hepatocellular carcinoma. The oral microbiota may serve as an endogenous reservoir for gut microbiota, and transport of oral bacteria through the gastro-intestinal tract can set up a gut microbiome dysbiosis. Gut dysbiosis increases the production of potential hepatotoxins, including lipopolysaccharide, ethanol, and other volatile organic compounds such as acetone, phenol and cyclopentane. Moreover, gut dysbiosis increases intestinal permeability by disrupting tight junctions in the intestinal wall, leading to enhanced translocation of these hepatotoxins and enteric bacteria into the liver through the portal circulation. In particular, many animal studies support that oral administration of Porphyromonas gingivalis, a typical periodontopathic bacterium, induces disturbances in glycolipid metabolism and inflammation in the liver with gut dysbiosis. NAFLD, also known as the hepatic phenotype of metabolic syndrome, is strongly associated with metabolic complications, such as obesity and diabetes. Periodontal disease also has a bidirectional relationship with metabolic syndrome, and both diseases may induce oral and gut microbiome dysbiosis with insulin resistance and systemic chronic inflammation cooperatively. In this review, we will describe the link between periodontal disease and NAFLD with a focus on basic, epidemiological, and clinical studies, and discuss potential mechanisms linking the two diseases and possible therapeutic approaches focused on the microbiome. In conclusion, it is presumed that the pathogenesis of NAFLD involves a complex crosstalk between periodontal disease, gut microbiota, and metabolic syndrome. Thus, the conventional periodontal treatment and novel microbiome-targeted therapies that include probiotics, prebiotics and bacteriocins would hold great promise for preventing the onset and progression of NAFLD and subsequent complications in patients with periodontal disease.

Effects of periodontal pathogen-induced intestinal dysbiosis on transplant immunity in an allogenic skin graft model.

Periodontal disease can induce dysbiosis, a compositional and functional alteration in the microbiota. Dysbiosis induced by periodontal disease is known to cause systemic inflammation and may affect transplant immunity. Here, we examined the effects of periodontal disease-related intestinal dysbiosis on transplant immunity using a mouse model of allogenic skin graft in which the mice were orally administered the periodontal pathogen Porphyromonas gingivalis (Pg). For 6 weeks, the Pg group orally received Pg while the control group orally received phosphate-buffered saline solution. After that, both groups received allogenic skin grafts. 16 s rRNA analysis of feces revealed that oral administration of Pg significantly increased three short chain fatty acids (SCFAs) producing genera. SCFA (acetate and propionate) levels were significantly higher in the Pg group (p = 0.040 and p = 0.005). The ratio of regulatory T cells, which are positively correlated with SCFAs, to total CD4+ T cells in the peripheral blood and spleen was significantly greater (p = 0.002 and p < 0.001) in the Pg group by flowcytometry. Finally, oral administration of Pg significantly prolonged skin graft survival (p < 0.001) and reduced pathological inflammation in transplanted skin grafts. In conclusion, periodontal pathogen-induced intestinal dysbiosis may affect transplant immunity through increased levels of SCFAs and regulatory T cells. (198 words).

Incision-free, coronally advanced flap with subepithelial connective tissue graft placed by the molar or canine access (MOCA) technique: 13 case series.

INTRODUCTION: Root coverage procedures are not always predictable, and outcomes depend on several factors. This technique provides a predictable alternative to managing facial gingival recessions. CASE SERIES: A new grafting technique is introduced that requires no incisions at the recipient site, thereby preserving the integrity of the local blood supply to optimize the healing process. The graft is placed through the gingival sulcus via a molar or canine access (MOCA) approach, and there is minimal tension on the coronally advanced flap through use of suspension sutures. Thirteen non-smoking patients, between the ages of 27 and 57, with Cairo RT1 facial recession were studied, with a follow-up period of 1-60 weeks. This paper explains the step-by-step technique and highlights 13 cases. CONCLUSION: Complete root coverage was achieved in all 13 cases, although one case showed initial altered healing. While MOCA is technique sensitive, it provides optimal root coverage results. With no incisions at the recipient site, there is no uneven texture or scar formation, and healing proceeds with minimal interruption. Why is this case series new information? MOCA is a unique approach to introduce grafts into non-incised sites of recession that can be one, two, or three teeth away at molars or canines. Non-incised approach minimizes interruption to blood supply. Coronally advanced flaps are secured in place with composite-fastened suspension sutures for tension-free flap closure. What are the keys to successful management of these cases? Good quality and quantity of connective tissue graft Early diagnosis and treatment of recession Expert surgical technique What are the key limitations to the success of these cases? The quality of the donor site is variable among patients. A technique-sensitive approach Advanced recession might warrant a second surgery.

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.

A Case of Necrotizing Periodontitis in a Care-Requiring Elderly Person Treated and Managed by Interprofessional Collaboration.

BACKGROUND: Necrotizing periodontitis (NP) is a reactive and destructive inflammatory process that occurs in response to bacterial infection. Predisposing factors such as compromised host immune responses contribute significantly to NP pathogenesis. NP occasionally progresses to a more advanced and life-threatening state. CASE PRESENTATION: A 73-year-old man in need of nursing care visited our dental clinic with severe gingival pain and intraoral bleeding. He had a disability and was immunocompromised because his medical history included cerebral infarction and type 2 diabetes mellitus. He was diagnosed with NP based on his typical symptoms, such as prominent bleeding and suppurative discharge from the gingiva, in addition to crater-shaped ulcerations of the interdental papillae. To improve daily oral hygiene, periodontists, dentists, and dental hygienists educated care workers and other staff at the nursing home on appropriate oral cleansing, including brushing three times a day using the Bass technique. Basic periodontal therapy, including whole-mouth scaling and debridement of the root surfaces using hand and ultrasonic instruments, was also performed. After this basic treatment of NP, we extracted the hopeless teeth. Currently, dentists visit the patient fortnightly to manage his oral hygiene. To date, good oral health has been maintained.

Wound healing in periodontal disease induces macrophage polarization characterized by different arginine-metabolizing enzymes.

BACKGROUND AND OBJECTIVE: Macrophages play important roles from the initiation of inflammation to wound healing. Two phenotypes of macrophages, namely pro-inflammatory type macrophages (M1-MΦ) and anti-inflammatory type macrophages (M2-MΦ), have been reported. Two contrasting metabolic enzymes that use arginine as a substrate, inducible nitric oxide synthase (iNOS), and arginase-1 (Arg-1), have been identified as M1-MΦ and M2-MΦ markers, respectively. The purpose of this study was to elucidate the temporal dynamics of the macrophage phenotype during the progression and healing phases of experimental periodontitis in mice. MATERIAL AND METHODS: A total of 63 C57BL/6J mice were divided into the following 3 groups: control (C), periodontitis (P), and healing (H). To induce periodontitis, a silk ligature was placed around the maxillary bilateral second molars of mice in the periodontitis and healing groups. In the healing group, the ligature was removed 3 days after ligation to induce tissue healing. Maxillary tissue was collected on day 0 for the control group, days 1, 3, 5, and 7 for the periodontitis group (P1, P3, P5, and P7), and days 5 and 7 for the healing group (H5 and H7: 3 days with the ligation + 2 days or 4 days following ligature removal). The left side of the maxilla was subjected to bone structure analysis using micro-computed tomography and gene expression analysis using polymerase chain reaction. On the right side, immunohistochemistry was performed to histopathologically evaluate the localization of macrophages by phenotype in the periodontal tissue. RESULTS: In the alveolar bone structure analysis, the linear distance of bone height increased significantly in the P5 and P7 groups, whereas bone volume fraction and bone mineral density decreased over time after ligature placement; in the healing group (H5 and H7), these parameters improved significantly compared with the periodontitis group (P5 and P7). Expression of genes encoding pro-inflammatory cytokines and iNOS increased in the periodontitis group, and expression of anti-inflammatory cytokine genes and Arg-1 increased in the healing group. Furthermore, the iNOS/Arg-1 expression ratio increased with ligation, whereas the ratio in the healing groups (H5 and H7) significantly decreased compared with the periodontitis groups (P5 and P7). Immunofluorescence staining revealed a significant increase in the number of iNOS-positive macrophages in the periodontitis group and decrease in the healing group. In contrast, the number of Arg-1-positive macrophages decreased in the periodontitis group and increased in the healing group. CONCLUSION: The results of the present study suggest that wound healing in periodontal disease induces macrophage polarization from M1-MΦ to M2-MΦ characterized by iNOS and Arg-1.

Periodontal disease-related nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: An emerging concept of oral-liver axis.

Periodontal disease, a chronic inflammatory disease of the periodontal tissues, is not only a major cause of tooth loss, but it is also known to exacerbate/be associated with various metabolic disorders, such as obesity, diabetes, dyslipidemia, and cardiovascular disease. Recently, growing evidence has suggested that periodontal disease has adverse effects on the pathophysiology of liver disease. In particular, nonalcoholic fatty liver disease, a hepatic manifestation of metabolic syndrome, has been associated with periodontal disease. Nonalcoholic fatty liver disease is characterized by hepatic fat deposition in the absence of a habitual drinking history, viral infections, or autoimmune diseases. A subset of nonalcoholic fatty liver diseases can develop into more severe and progressive forms, namely nonalcoholic steatohepatitis. The latter can lead to cirrhosis and hepatocellular carcinoma, which are end-stage liver diseases. Extensive research has provided plausible mechanisms to explain how periodontal disease can negatively affect nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, namely via hematogenous or enteral routes. During periodontitis, the liver is under constant exposure to various pathogenic factors that diffuse systemically from the oral cavity, such as bacteria and their by-products, inflammatory cytokines, and reactive oxygen species, and these can be involved in disease promotion of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Also, gut microbiome dysbiosis induced by enteral translocation of periodontopathic bacteria may impair gut wall barrier function and promote the transfer of hepatotoxins and enterobacteria to the liver through the enterohepatic circulation. Moreover, in a population with metabolic syndrome, the interaction between periodontitis and systemic conditions related to insulin resistance further strengthens the association with nonalcoholic fatty liver disease. However, most of the pathologic links between periodontitis and nonalcoholic fatty liver disease in humans are provided by epidemiologic observational studies, with the causal relationship not yet being established. Several systematic and meta-analysis studies also show conflicting results. In addition, the effect of periodontal treatment on nonalcoholic fatty liver disease has hardly been studied. Despite these limitations, the global burden of periodontal disease combined with the recent nonalcoholic fatty liver disease epidemic has important clinical and public health implications. Emerging evidence suggests an association between periodontal disease and liver diseases, and thus we propose the term periodontal disease-related nonalcoholic fatty liver disease or periodontal disease-related nonalcoholic steatohepatitis. Continued efforts in this area will pave the way for new diagnostic and therapeutic approaches based on a periodontologic viewpoint to address this life-threatening liver disease.

The human oral virome: Shedding light on the dark matter.

Mediators of the initiation, development, and recurrence of periodontitis include the oral microbiome embedded in subgingival plaque and the host immune response to a dysbiosis within this dynamic and complex microbial community. Although mediators have been studied extensively, researchers in the field have been unable to fully ascribe certain clinical presentations of periodontitis to their nature. Emergence of high-throughput sequencing technologies has resulted in better characterization of the microbial oral dysbiosis that extends beyond the extensively studied putative bacterial periodontopathogens to a shift in the oral virome composition during disease conditions. Although the biological dark matter inserted by retroviruses was once believed to be nonfunctional, research has revealed that it encodes historical viral-eukaryotic interactions and influences host development. The objective of this review is to evaluate the proposed association of herpesviruses to the etiology and pathogenesis of periodontal disease and survey the highly abundant prokaryotic viruses to delineate their potential roles in biofilm dynamics, as well as their interactions with putative bacterial periodontopathogens and eukaryotic cells. The findings suggest that potential novel periodontal therapies targeting or utilizing the oral virome can alleviate certain clinical presentations of periodontitis. Perhaps it is time to embrace the viral dark matter within the periodontal environment to fully comprehend the pathogenesis and systemic implications of periodontitis.

Rebuilding the Interproximal Papilla: Description of "Tube" Technique and Two Case Reports.

INTRODUCTION: Papilla reconstruction relies on similar principles as those applied to soft tissue grafting for recession defects; however, it is uniquely challenging from a surgical perspective because of the small size and lack of a blood supply. Several techniques have been used to reconstruct lost papilla; however, there are no prescribed techniques for this specific application. CASE PRESENTATION: This report describes a novel technique, herein called, the "tube technique" for treating interproximal recession and reconstructing the interproximal papilla, and documents two cases using the tube technique. An increase in attachment levels was observed in Case 1 (5 mm) and in Case 2 (4 mm) after using this surgical technique for papilla reconstruction. CONCLUSION: The tube grafting technique requires technical precision. Although when executed carefully, it results in predictable reconstruction of the interproximal papilla. Use of the tube technique helps mitigate issues associated with inadequate flap thickness, blood supply, and flap retraction.

Periodontal inflammation triggers a site-specific and wide radius of calcium metabolic effects on alveolar bone.

BACKGROUND AND OBJECTIVE: There is a close relationship between inflammation and bone remodeling in the periodontium. However, previous studies have not delineated the alterations in calcium (Ca) metabolism during periodontitis progression. The aim of this current investigation was to examine Ca dynamics in alveolar bone of rats during progression of ligature-induced periodontal inflammation by using 45 Ca, which is an index of hard tissue neogenesis. MATERIAL AND METHODS: To induce periodontitis, the maxillary right first molar (M1) of 8-week-old male rats was ligated with a silk suture for 1, 3, 7, and 28 days. The left M1 was not ligated as a control. To evaluate resultant changes in bone neogenesis, 45 CaCl2 was injected intraperitoneally 24 hours before euthanasia. The left-and-right palatal mucosa, molar teeth (M1 and M2), and alveolar bone were harvested for evaluation of 45 Ca radioactivity using a liquid scintillation counter. The distribution of 45 Ca in maxillary tissues was evaluated using autoradiography (ARG). In addition, we analyzed the bone volume fraction (BV/TV) and bone mineral density (BMD) of the alveolar bone by micro-computed tomography. To investigate the number of osteoclasts and osteoblasts, tartrate-resistant acid phosphatase (TRAP) and bone-specific alkaline phosphatase (BAP) were measured by an enzymatic assay and immunohistochemistry, respectively. RESULTS: 45 Ca radioactivity in the alveolar bone of the ligature side decreased by 8% compared to the unligated control-side on day 1, whereas on day 7, it markedly increased by 33%. The 45 Ca levels in the gingival tissue and molar teeth were slightly but significantly lower than the control-side on day 1 and higher from day 3 to 28. The variation in 45 Ca levels for the alveolar bone was greater and specific compared with other tissues. Furthermore, on day 7, ARG data revealed that 45 Ca on the control side was primarily localized to the periodontal ligament (PDL) space and alveolar bone crest and barely detected in the gingival tissues and deeper parts of the alveolar bone. On the ligature side, 45 Ca disappeared from the PDL and alveolar crest, but instead was broadly and significantly increased within the deeper zones of the alveolar bone and furcation areas and distant from the site of ligature placement and periodontal inflammation. In the shallow zone of the alveolar bone, these changes in 45 Ca levels on day 7 were consistent with decreases in the bone structural parameters (BV/TV and BMD), enhanced osteoclast presence, and suppressed levels of BAP expression in osteoblasts. In contrast, the deep zone and furcation area showed that TRAP-positive cells increased, but BAP expression was maintained in the resorption lacunae of the alveolar bone. CONCLUSION: During periodontitis progression in rats, 45 Ca levels in the alveolar bone exhibited biphasic alterations, namely decreases and increases. These data indicate that periodontitis induces a wide range of site-specific Ca metabolism alterations within the alveolar bone.

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.

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.

Relationship between periodontal parameters and non-vital pulp in dental clinic patients: a cross-sectional study.

BACKGROUND: Endodontic diseases, such as apical periodontitis, communicate with periodontitis and mutually exacerbate them. However, it remains unclear whether pulp condition is a risk factor for periodontal disease. The purpose of this retrospective study was to examine relations between pulp condition and periodontal parameters in Japanese patients who visited a general dental clinic. METHODS: Patients who visited a Japanese general dental clinic from 2016 to 2018 and aged 18 to 81 years were analyzed. Periodontal parameters, tooth condition, and general status of all teeth excluding third molars at the initial visit to the clinic were abstracted. A total of 7105 teeth were analyzed in this study by multiple classification analysis and the Mann-Whitney U test. We also performed a sub-analysis of non-vital teeth, which evaluated the presence or absence of unfavorable root canal obturation and apical periodontitis diagnosed by X-ray. RESULTS: Significant relations between periodontal parameters and non-vital pulp were observed by multiple logistic regression analyses (odds ratio = 1.48; 95% CI = 1.03-2.14) and multiple linear regression analysis (p < 0.001). Significant relations between unfavorable root canal obturation tooth with periodontal pocket depth (p = 0.00837) and BOP (p = 0.0145) were also observed by the Mann-Whitney U test. CONCLUSIONS: We demonstrated potential relations between periodontal disease and non-vital pulp.

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.

Temporal and dynamic changes in gingival blood flow during progression of ligature-induced periodontitis.

OBJECTIVES: To evaluate temporal changes in gingival blood flow (GBF) during progression of periodontitis in rats using a laser Doppler flowmeter (LDF) approach and to characterize morphological and biochemical features in the periodontium associated with GBF. MATERIALS AND METHODS: Forty-two Wistar rats were divided into a ligature-induced periodontitis group and a control group. To induce periodontitis, ligatures were tied around maxillary first molars bilaterally. GBF was measured in palatal gingiva at pretreatment and following ligature placement after 30 min, 1, 3, 7, 14, 21, and 28 days using LDF with a non-contact probe. Bone loss and gene expression in gingival tissues were assessed using micro-computed tomography (µCT) and quantitative polymerase chain reaction (PCR), respectively. Immunostaining for vascular endothelial growth factor (VEGF) in the maxilla was also histologically evaluated. RESULTS: GBF in the ligature group increased significantly compared with the control group 30 min after ligation. However, on days 3 and 7, GBF decreased in the ligature group. Also, after day 10, there was no difference in GBF between groups. The levels of alveolar bone loss, gene expression (interleukin-6, cluster of differentiation-31, VEGF-A, and lymphatic vessel endothelial hyaluronan receptor-1), and immunostained VEGF-positive vessels correlated well with changes in GBF. CONCLUSION PROGRESSION OF PERIODONTITIS: In rats was associated with a triphasic pattern of GBF, consisting of a short initial increase, followed by a rapid decrease, and then a gradual plateau phase.