Metabolomics analysis in saliva from periodontally healthy, gingivitis and periodontitis patients.

OBJECTIVE: The aim of this study was to investigate metabolomics markers in the saliva of patients with periodontal health, gingivitis and periodontitis. BACKGROUND: The use of metabolomics for diagnosing and monitoring periodontitis is promising. Although several metabolites have been reported to be altered by inflammation, few studies have examined metabolomics in saliva collected from patients with different periodontal phenotypes. METHODS: Saliva samples collected from a total of 63 patients were analysed by nuclear magnetic resonance (NMR) followed by ELISA for interleukin (IL)-1ß. The patient sample, well-characterised clinically, included periodontal health (n = 8), gingivitis (n = 19) and periodontitis (n = 36) cases, all non-smokers and not diabetic. RESULTS: Periodontal diagnosis (healthy/gingivitis/periodontitis) was not associated with any salivary metabolites in this exploratory study. Periodontal staging showed nominal associations with acetoin (p = .030) and citrulline (p = .047). Among other investigated variables, the use of systemic antibiotics in the previous 3 months was associated with higher values of the amino acids taurine, glycine and ornithine (p = .002, p = .05 and p = .005, respectively, at linear regression adjusted for age, gender, ethnicity, body mass index and staging). CONCLUSION: While periodontal staging was marginally associated with some salivary metabolites, other factors such as systemic antibiotic use may have a much more profound effect on the microbial metabolites in saliva. Metabolomics in periodontal disease is still an underresearched area that requires further observational studies on large cohorts of patients, aiming to obtain data to be used for clinical translation.

Repurposing Metformin for periodontal disease management as a form of oral-systemic preventive medicine.

BACKGROUND: Despite the improvements in treatment over the last decades, periodontal disease (PD) affects millions of people around the world and the only treatment available is based on controlling microbial load. Diabetes is known to increase the risk of PD establishment and progression, and recently, glucose metabolism modulation by pharmaceutical or dietarian means has been emphasised as a significant modulator of non-communicable disease development. METHODS: The impact of pharmaceutically controlling glucose metabolism in non-diabetic animals and humans (REBEC, UTN code: U1111-1276-1942) was investigated by repurposing Metformin, as a mean to manage periodontal disease and its associated systemic risk factors. RESULTS: We found that glucose metabolism control via use of Metformin aimed at PD management resulted in significant prevention of bone loss during induced periodontal disease and age-related bone loss in vivo. Metformin also influenced the bacterial species present in the oral environment and impacted the metabolic epithelial and stromal responses to bacterial dysbiosis at a single cell level. Systemically, Metformin controlled blood glucose levels and age-related weight gain when used long-term. Translationally, our pilot randomized control trial indicated that systemic Metformin was safe to use in non-diabetic patients and affected the periodontal tissues. During the medication window, patients showed stable levels of systemic blood glucose, lower circulating hsCRP and lower insulin levels after periodontal treatment when compared to placebo. Finally, patients treated with Metformin had improved periodontal parameters when compared to placebo treated patients. CONCLUSION: This is the first study to demonstrate that systemic interventions using Metformin in non-diabetic individuals aimed at PD prevention have oral-systemic effects constituting a possible novel form of preventive medicine for oral-systemic disease management.

Is subclinical cardiovascular disease linked with periodontal disease in diabetic and non-diabetic subjects?

Periodontal disease leads to a systemic hyper-inflammatory state that might impair other co-morbidities including cardiovascular disease. Evidence-based findings showed that periodontitis may be linked with subclinical signs of cardiovascular diseases such as arterial stiffness. Nevertheless, some contrasting results have been reported over the years. A cross-sectional study regarding the relationship between periodontal disease and subclinical cardiovascular diseases, in non-diabetic and diabetic individuals, has been recently published. Therefore, the aim of this commentary is to give an in-depth on this topic.

Could dietary restrictions affect periodontal disease? A systematic review.

OBJECTIVE: This review aimed at evaluating the possible benefits that caloric restriction (CR) may provide to periodontal disease progression and response to treatment. MATERIAL AND METHODS: Electronic search on Medline, Embase and Cochrane, and manual search were performed to identify pre-clinical and on human studies reporting the consequences of CR on clinical and inflammatory parameters related to periodontitis. Newcastle Ottawa System and SYRCLE scale were used to assess the risk of bias. RESULTS: Four thousand nine hundred eighty articles were initially screened, and a total of 6 articles were finally included, consisting of 4 animal studies and 2 studies in humans. Due to the limited number of studies and heterogeneity of the data, results were presented in descriptive analyses. All studies showed that, compared to the normal (ad libitum) diet, CR might have the potential to reduce the local and systemic hyper-inflammatory state as well as disease progression in periodontal patients. CONCLUSIONS: Within the existing limitations, this review highlights that CR showed some improvements in the periodontal condition by reducing the local and systemic inflammation related to the periodontitis and by improving clinical parameters. However, the results should be interpreted with caution since robust research such as randomized clinical trials is still missing. CLINICAL RELEVANCE: This review shows that some dietary/caloric restrictions approaches may have the potential to improve periodontal conditions and, in addition, highlights a need for human studies with a robust methodology in order to draw stronger evidence-based conclusions.

Biomarker Expression of Peri-Implantitis Lesions before and after Treatment: A Systematic Review.

The need to predict, diagnose and treat peri-implant diseases has never been greater. We present a systematic review of the literature on the changes in the expression of biomarkers in peri-implant crevicular fluid (PICF) before and after treatment of peri-implantitis. Bacterial composition, clinical and radiographic parameters, and systemic biomarkers before and after treatment are reported as secondary outcomes. A total of 17 studies were included. Treatment groups were non-surgical treatment or surgical treatment, either alone or with adjunctive therapy. Our findings show that non-surgical treatment alone does not influence biomarker levels or clinical outcomes. Both adjunctive photodynamic therapy and local minocycline application resulted in a reduction of interleukin (IL)-1ß and IL-10 twelve months after treatment. Non-surgical treatments with adjunctive use of lasers or antimicrobials were more effective at improving the clinical outcomes in the short-term only. Access flap debridement led to matrix metalloproteinase (MMP)-8 and tumour necrosis factor-α reduction twelve months post-surgery. Surgical debridement with adjunctive antimicrobials achieved a decrease in MMP-8 at three months. Adjunctive use of Emdogain™ (EMD) was associated with a reduction in 40 PICF proteins compared to access flap surgery alone. Surgical interventions were more effective at reducing probing pocket depth and bleeding on probing both in the short- and long-term. Surgical treatment in combination with EMD was found to be more effective in resolving inflammation up to twelve months.

Periodontitis and implant complications in diabetes.

Epidemiologic evidence indicates that periodontitis is more frequent in patients with uncontrolled diabetes mellitus than in healthy controls, suggesting that it could be considered the "sixth complication" of diabetes. Actually, diabetes mellitus and periodontitis are two extraordinarily prevalent chronic diseases that share a number of comorbidities all converging toward an increased risk of cardiovascular disease. Periodontal treatment has recently been shown to have the potential to improve the metabolic control of diabetes, although long-term studies are lacking. Uncontrolled diabetes also seems to affect the response to periodontal treatment, as well as the risk to develop peri-implant diseases. Mechanisms of associations between diabetes mellitus and periodontal disease include the release of advanced glycation end products as a result of hyperglycemia and a range of shared predisposing factors of genetic, microbial, and lifestyle nature. This review discusses the evidence for the risk of periodontal and peri-implant disease in diabetic patients and the potential role of the dental professional in the diabetes-periodontal interface.

Managing the Systemic Impact of Periodontitis.

Periodontitis is a microbially driven host-mediated disease that leads to loss of periodontal attachment and bone. It is associated with elevation of systemic inflammatory markers and with the presence of systemic co-morbidities. Furthermore, periodontal treatment leads to a 24-48 h-long acute local and systemic inflammatory response. This systemic response might increase the burden of patients with compromised medical history and/or uncontrolled systemic diseases. The correlation between periodontitis and systemic diseases, the impact of periodontitis on the quality of life and public health, the effects of periodontal treatment on systemic health and disease, and the available methods to manage systemic inflammation after periodontal therapy are discussed. The main focus then shifts to a description of the existing evidence regarding the impact of periodontitis and periodontal treatment on systemic health and to the identification of approaches aiming to reduce the effect of periodontitis on systemic inflammation.

A New Comorbidity in Periodontitis: Fusobacterium nucleatum and Colorectal Cancer.

There is very recent and strong evidence relating Fusobacterium nucleatum to colorectal cancer. In this narrative review, we update the knowledge about gingival dysbiosis and the characteristics of Fusobacterium nucleatum as one of the main bacteria related to periodontitis. We provide data on microbiome, epidemiology, risk factors, prognosis, and treatment of colorectal cancer, one of the most frequent tumours diagnosed and whose incidence increases every year. We describe, from its recent origin, the relationship between this bacterium and this type of cancer and the knowledge and emerging mechanisms that scientific evidence reveals in an updated way. A diagram provided synthesizes the pathogenic mechanisms of this relationship in a comprehensive manner. Finally, the main questions and further research perspectives are presented.

Keratinized mucosa changes around one-stage implants: A prospective case series.

BACKGROUND: The need of an adequate band of keratinized tissue (KT) to maintain periodontal health around teeth as well as around implants has been a debated topic over many years but still no conclusions have been drawn. OBJECTIVES: This prospective case series evaluates the changes undergone by the keratinized mucosa (KM) and the soft tissue volume around non-submerged implants before the prosthetic rehabilitation. MATERIAL AND METHODS: A total of 40 patients were included. The primary outcome was to analyze the width of the KM at both buccal and lingual aspects compared to the pre-existing KT in the edentulous ridge only in mandibular (pre)molar area. The mucogingival line was marked with a surgical pen and an intra-oral scanner was used to take the impression of the implant area the day of the surgery (T0, baseline) and before the crown placement (T1, 3 months). Buccal soft tissue volume was measured at 1, 3, and 5 mm apical to the healing abutment position and a comparison between T0 and T1 was performed. Student t-test was used according to the distribution of the data (Shapiro-Wilk). RESULTS: The mean KT width at baseline was 4.54 ± 1.31 mm at buccal side and 5.04 ± 1.88 mm at lingual side. After 3 months, the mean KM values were 3.15 ± 1.03 mm and 3.72 ± 1.56 mm at the buccal and lingual aspects, respectively. The differences, 30.6% of KM reduction buccally and 26.1% of reduction lingually, were statistically significant for both sides. CONCLUSIONS: Within the limitations of this investigation, it was observed that the KM width from the baseline to the 3 months follow up presented a significant dimensional change in both the buccal and lingual aspects, whereas buccal soft tissue volume showed an increase between baseline and follow up.

Associations between Periodontitis, COVID-19, and Cardiometabolic Complications: Molecular Mechanisms and Clinical Evidence.

Periodontitis is a microbially driven, host-mediated disease that leads to loss of periodontal attachment and resorption of bone. It is associated with the elevation of systemic inflammatory markers and with the presence of systemic comorbidities. Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the majority of patients have mild symptoms, others experience important complications that can lead to death. After the spread of the COVID-19 pandemic, several investigations demonstrating the possible relationship between periodontitis and COVID-19 have been reported. In addition, both periodontal disease and COVID-19 seem to provoke and/or impair several cardiometabolic complications such as cardiovascular disease, type 2 diabetes, metabolic syndrome, dyslipidemia, insulin resistance, obesity, non-alcoholic fatty liver disease, and neurological and neuropsychiatric complications. Therefore, due to the increasing number of investigations focusing on the periodontitis-COVID-19 relationship and considering the severe complications that such an association might cause, this review aims to summarize all existing emerging evidence regarding the link between the periodontitis-COVID-19 axis and consequent cardiometabolic impairments.

Compliance with supportive periodontal/peri-implant therapy: A systematic review.

AIM: The present systematic review aimed at assessing the degree of compliance with supportive periodontal/peri-implant therapy as well as identifying patient-related factors that could potentially play a role on patient compliance. METHODS: Electronic and manual literature searches were carried out to assess patient compliance during maintenance. Main outcomes were compliance definition, degree of compliance and patient-related factors. Owing to the heterogeneity of the data reported across the studies, descriptive statistics were performed to shed light on compliance rate and the patient-related factors. RESULTS: A total of 39 articles were included. No consensus regarding the definition of "compliance" was found in the analysed literature. The percentage of fully compliers and non-compliers ranged between 3.3%-86.8% and 1.69%-64.4%, respectively. Smoking habit and history of periodontal disease were found to be associated with patients' compliance. Inadequate information/motivation was found as the main patient-reported reason for non-compliance. CONCLUSIONS: Despite the high variability across studies, compliance with the supportive periodontal/peri-implant maintenance therapy was found to be unsatisfactory. Attitudes, psychological traits and construct associated with compliance remain largely unknown, and still, lack of information and motivation are paramount to be addressed during the periodontal/implant therapy to increase patient compliance.