Evaluation of microbiome in primary and permanent dentition in grade C periodontitis in young individuals.

BACKGROUND: The aim of the present study was to evaluate the subgingival microbiome in patients with grade C molar-incisor pattern periodontitis (C-MIP) affecting the primary or permanent dentitions. METHODS: DNA was isolated from subgingival biofilm samples from diseased and healthy sites from 45 C-MIP patients and subjected to phylogenetic microarray analysis. C-MIP sites were compared between children affected in the primary to those affected in the permanent dentitions. Within-subject differences between C-MIP-affected sites and dentition-matched healthy sites were also evaluated. RESULTS: C-MIP sites of subjects affected in the primary dentition showed partially overlapping but distinct microbial communities from C-MIP permanent dentition sites (p < 0.05). Differences were due to increased levels in primary C-MIP sites of certain species of the genera Capnocytophaga and Leptotrichia, while C-MIP permanent dentition sites showed higher prevalence of Filifactor alocis. Aggregatibacter actinomycetemcomitans (Aa) was among species seen in high prevalence and levels in both primary and permanent C-MIP sites. Moreover, both permanent and primary C-MIP sites showed distinct microbial communities when compared to dentition-matched healthy sites in the same subject (p < 0.01). CONCLUSIONS: Primary and permanent teeth with C-MIP showed a dysbiotic microbiome, with children affected in the primary dentition showing a distinct profile from those affected in the permanent dentition. However, Aa was enriched in both primary and permanent diseased sites, confirming that this microorganism is implicated in C-MIP in both dentitions.

Distinctive genes and signaling pathways associated with type 2 diabetes-related periodontitis: Preliminary study.

The biological mechanisms underlying the pathogenesis of type 2 diabetes (T2DM)-related periodontitis remain unclear. This cross-sectional study evaluated the distinctive transcriptomic changes between tissues with periodontal health and with periodontitis in patients with T2DM. In this cross-sectional study, whole transcriptome sequencing was performed on gingival biopsies from non-periodontitis and periodontitis tissues from non-diabetic and diabetic patients. A differentially expressed gene (DEG) analysis and Ingenuity Pathway Analysis (IPA) assessed the genes and signaling pathways associated with T2DM-related periodontitis. Immunohistochemistry was performed to validate selected DEGs possibly involved in T2DM-related periodontitis. Four hundred and twenty and one thousand five hundred and sixty-three DEGs (fold change ≥ 2) were uniquely identified in the diseased tissues of non-diabetic and diabetic patients, respectively. The IPA predicted the activation of Phagosome Formation, Cardiac ß-adrenergic, tRNA Splicing, and PI3K/AKT pathways. The IPA also predicted the inhibition of Cholesterol Biosynthesis, Adrenomedullin, and Inositol Phosphate Compounds pathways in T2DM-related periodontitis. Validation of DEGs confirmed changes in protein expression of PTPN2, PTPN13, DHCR24, PIK3R2, CALCRL, IL1RN, IL-6R and ITGA4 in diseased tissues in diabetic subjects. Thus, these preliminary findings indicate that there are specific genes and functional pathways that may be involved in the pathogenesis of T2DM-related periodontitis.

Association of Physical Frailty and Cognitive Function in a Population-Based Cross-Sectional Study of American Older Adults.

INTRODUCTION: Cognitive impairment and frailty are prevalent in older persons. Physical frailty is associated with cognitive decline; however, the role of effect modifiers such as age, sex, race/ethnicity, and cognitive reserve is not well understood. METHODS: Cross-sectional data from the National Health and Nutrition Examination Survey (2011-2014) were obtained for participants aged ≥60 years. Complete availability of cognitive scores was an inclusion criterion. Physical frailty was defined by the presence of exhaustion, weakness, low body mass, and/or low physical activity, and categorized into three groups: robust (0 present), pre-frail (1-2 present), or frail (3-4 present). Four cognitive test scores were converted to z-scores, and global cognition (composite z-score) was calculated by averaging the four-individual z-scores. Multivariable linear regression models were fit to estimate the associations between frailty and cognitive function. Frailty was also evaluated as a risk factor for self-reported subjective memory complaint (SMC) using logistic regression. All models were adjusted for age, sex, race/ethnicity, education, alcohol use, income, marital status, diabetes, hypertension, and history of stroke. Effect measure modification analyses were conducted by age, sex, race/ethnicity, education, and occupational cognitive demand. RESULTS: The study population comprised 2,863 participants aged ≥60 years. 50.6% of the participants were categorized into robust, 43.2% pre-frail, and 6.2% frail. After adjusting for covariates, compared to robust participants, frail and prefrail participants had lower adjusted mean global cognitive z-scores, ß^ = -0.61, 95% CI: -0.83, -0.38 and ß^ = -0.21, 95% CI: -0.30, -0.12, respectively. Both prefrail and frail participants had higher odds of SMC compared to the robust participants. We did not see strong evidence that the association between frailty and cognition was modified by the factors we studied. DISCUSSION/CONCLUSION: Both pre-frailty and frailty were associated with lower cognitive performance and were more likely to report subjective memory complaints relative to persons without frailty. These findings provide additional evidence that physical frailty may serve as a prognostic factor for cognitive deterioration or dementia, and prevention of frailty may be an important public health strategy.

FBXO11 regulates bone development.

FBXO11 is the substrate-recognition component of a ubiquitin ligase complex called SKP1-cullin-F-boxes. The role of FBXO11 in bone development is unexplored. In this study, we reported a novel mechanism of how bone development is regulated by FBXO11. FBXO11 gene knockdown by lentiviral transduction in mouse pre-osteoblast MC3T3-E1 cells leads to reduced osteogenic differentiation, while overexpressing FBXO11 accelerates their osteogenic differentiation in vitro. Furthermore, we generated two osteoblastic-specific FBXO11 conditional knockout mouse models, Col1a1-ERT2-FBXO11KO and Bglap2-FBXO11KO mice. In both conditional FBXO11KO mouse models, we found FBXO11 deficiency inhibits normal bone growth, in which the osteogenic activity in FBXO11cKO mice is reduced, while osteoclastic activity is not significantly changed. Mechanistically, we found FBXO11 deficiency leads to Snail1 protein accumulation in osteoblasts, leading to suppression of osteogenic activity and inhibition of bone matrix mineralization. FBXO11 knockdown in MC3T3-E1 cells reduced Snail1 protein ubiquitination and increased Snail1 protein accumulation in the cells, which eventually inhibited osteogenic differentiation. In conclusion, FBXO11 deficiency in osteoblasts inhibits bone formation through Snail1 accumulation, inhibiting osteogenic activity and bone mineralization.

Pattern of grade C molar-incisor pattern periodontitis in families.

BACKGROUND: The aim of this study was to determine the clinical and inflammatory response patterns for individual siblings diagnosed with grade C molar-incisor pattern periodontitis (C-MIP) and between the related siblings within families. METHODS: Sixty-nine siblings within 28 families with moderate-to-severe C-MIP were included. Clinical parameters were evaluated for symmetry regarding the affected type of teeth, side and/or arch, and bone loss pattern. The protein concentrations from in vitro whole blood cultures for 14 different lipopolysaccharide-stimulated inflammatory markers were correlated with the extent and severity of disease, within an individual sibling and among siblings within a family. RESULTS: A similar disease pattern was observed among all siblings and within families. The most common teeth affected were first molars and incisors or first molars only within the permanent dentition and only molars within the primary dentition (p < 0.001). Symmetry involving molars was higher than in incisors in siblings, regardless of arch or side affected (p = 0.020). Arc-shape/vertical bone defects were the most common (p = 0.006) and higher symmetry was found for these defects in the permanent dentition (p = 0.005). Positive correlations were found between age, clinical attachment loss, and percent affected sites with several inflammatory markers. The inflammatory responses for several inflammatory markers were correlated within and among families (p < 0.050). Specifically, the intraclass correlation coefficient within families was highest (>0.5) for interleukin (IL)-8, IL-6, and IL-10. CONCLUSIONS: Families with C-MIP presented similar patterns of disease. The level of an inflammatory response to bacteria seemed to play a role in the extent and severity of this disease, exemplified by the high degree of correlation in these families.

A randomized controlled trial to evaluate the effectiveness of a novel mouth rinse in patients with gingivitis.

BACKGROUND: This single-center, randomized controlled trial aimed to determine the effectiveness of a novel, biofilm-disrupting, mouth rinse that combines Cetylpyridinium chloride (CPC) and essential oils in preventing re-accumulation of supragingival plaque and supragingival microbiome in patients with gingivitis after dental prophylaxis. METHODS: One hundred eighteen participants were randomly assigned in a 1:1 ratio to receive twice-daily test mouth rinse (59) or carrier rinse control (59) for 12 weeks after dental prophylaxis. RESULTS: In a per-protocol analysis that included patients who completed the intervention, the treatment group (39) had significantly lower supragingival plaque scores at 6 and 12 weeks compared to the control group (41; p = 0.022). Both groups showed similar improvement in gingivitis score, but neither group had improvement in bleeding score or probing depth. Thirty-eight (29%) patients did not complete the study due to loss of follow-up (17) or early discontinuation of the assigned intervention (21). Microbiome sequencing showed that the treatment rinse significantly depleted abundant and prevalent members of the supragingival plaque microbiome consortium. CONCLUSIONS: Among patients with gingivitis, the novel mouth rinse significantly reduced re-accumulation of supragingival plaque following dental prophylaxis by depleting supragingival plaque microbiome. However, long-term adherence to the rinse may be limited by adverse effects ( ClinicalTrials.gov number, NCT03154021).

Gender differences in immunological response of African-American juveniles with Grade C molar incisor pattern periodontitis.

BACKGROUND: Prevalence of Grade C molar incisor periodontitis (C/MIP) in females (F) and males (M) is controversial, although some studies suggest higher prevalence in females. The objective of this study was to evaluate differences in clinical parameters, and levels of cyto/chemokines in gingival crevicular fluid (GCF) and peripheral blood response. METHODS: GCF and blood were collected from 79 C/MIP African-American participants (53F and 26 M) and healthy controls (58F and 38 M), aged 5 to 23. Blood was stimulated with ultrapure LPS from Escherichia coli (Ec) and Porphyromonas gingivalis (Pg) and we quantified levels of 14 cyto/chemokines. Clinical parameters were collected before and 12 months following treatment RESULTS: No clinical parameters or age differences were found between males and females, although age was negatively correlated with response to treatment. GCF levels of TNFα, IFNγ, MIP1α, and MCP1 from diseased and sites and healthy sites IFNγ levels were higher in M (P < 0.05). C/MIP females presented higher Pg and Ec LPS induced levels of Eotaxin, IFNγ, and GMCSF (P < 0.05), whereas healthy males presented higher Ec LPS induced levels of Eotaxin and IFNγ (P < 0.05). Inflammatory profiles were also different among genders in disease (P = 0.004). CONCLUSIONS: Although males seemed to present few elevated inflammatory markers in the GCF in disease and in health, females presented an elevated systemic inflammatory response to LPS in disease, which indicates a possible differential susceptibility to inflammation. Future studies need to determine if sex hormones have a role in the peripheral host response and in the pathogenesis of C/MIP.

Association of different antidepressant classes with clinical attachment level and alveolar bone loss in patients with periodontitis: A retrospective study.

OBJECTIVE: Our study aimed to determine the relationship of antidepressant medicine use with periodontal diseases, exploring the association of different pharmacological classes of antidepressant with observations of clinical attachment loss (CAL) and alveolar bone level (BL) in patients with periodontitis. BACKGROUND: Existing evidence on the impact of antidepressant medication on periodontal tissues has focused on some classes only and is still unclear. Therefore, this retrospective study evaluated the association of different antidepressant classes with clinical attachment loss (CAL) and alveolar bone level (BL). METHODS: This study was carried out in a population of patients aged ≥ 30 years old with periodontitis who sought treatment at the University of Florida from 2014 to 2018. The following variables were obtained from patients' records; usage of antidepressant medications and their pharmacological classes (selective serotonin reuptake inhibitors [SSRI], serotonin-norepinephrine reuptake inhibitors [SNRI], tricyclic, atypical, and monoamine oxidase inhibitors [MAO]), age, gender, smoking habit, mild systemic diseases, CAL, and cement-enamel junction (CEJ) and alveolar bone crest (BC) distance, defined as BL, in the Ramfjord index teeth. RESULTS: Five hundred and eighty-two periodontitis patients were evaluated, of which 113 (19.4%) were antidepressant users. Antidepressant users exhibited significantly lower BL and fewer sites with severe CAL (≥5 mm), than non-users (p < .05). Among all single-class antidepressant users, the SSRI users showed significantly less CAL and lower BL than non-users (p < .05). Patients taking combinations of the different classes of antidepressants also showed better CAL and BL than non-users. Generalized linear models, including variables such as gender, age, systemic diseases, and smoking, demonstrated that antidepressant users were more likely to have lower mean BL and fewer sites with severe bone loss (i.e. BL > 3 and >5 mm) than non-users (p < .05). CONCLUSIONS: Antidepressant medications were associated with higher alveolar bone level and less clinical attachment loss in patients with periodontitis. When the different classes of antidepressants were analyzed individually, only the SSRI class users and the multiple-class users showed significantly less periodontal breakdown than non-users.

Effects of different antidepressant classes on dental implant failure: A retrospective clinical study.

BACKGROUND: Previous studies have suggested an association between taking antidepressants and dental implant failure. This study aimed to investigate the association of different antidepressant classes with dental implant failure. METHODS: This retrospective study included patients that received dental implants at the University of Florida from 2011 to 2016. The variables of implant failure, antidepressant use and classes (selective serotonin reuptake inhibitors [SSRI], serotonin-norepinephrine reuptake inhibitors [SNRI], tricyclic antidepressants [TCA], atypical antidepressants [AA], and monoamine oxidase inhibitors [MAOI]), age, sex, smoking, mild systemic diseases, and implant location were obtained from patients' records. Odds ratio (OR) and confidence interval (CI) of implant failure in patients taking different antidepressant classes, in relationship to non-antidepressant users, were estimated, and the influence of multiple variables on implant failure were investigated. RESULTS: A total of 771 patients and 1,820 implants were evaluated. The statistically significant predictors for implant failure included smoking (OR = 5.221), use of antidepressants (OR = 4.285), posterior maxilla location (OR = 2.911), mild systemic disease (OR = 2.648), and age (OR = 1.037) (P <0.05). The frequency of implant failure was 33.3% in TCA users, 31.3% in SNRI users, 6.3% in SSRI users, 5.2% in Atypical antidepressant users, and 3.9% in non-users. Significant associations were observed between the use of SNRI (OR: 11.07; 95% CI: 3.265 to 33.82) and TCA (OR: 12.16; 95% CI: 1.503 to 71.58) and implant failure (P <0.05). CONCLUSIONS: Users of antidepressants were at higher risk of implant failure than non-users. Patients taking SNRI and TCA were at the highest risk of implant loss, when compared with non-users. Conclusions about TCA, however, are based on a limited number of cases.

Treatment of localized aggressive periodontitis alters local host immunoinflammatory profiles: A long-term evaluation.

AIM: To evaluate the local immunoinflammatory profiles in localized aggressive periodontitis patients (LAP) before and after periodontal treatment and maintenance. METHODS: Sixty-six African-Americans with LAP (7-21 years old) were included. After periodontal examination, all patients received periodontal treatment with mechanical debridement plus systemic amoxicillin/metronidazole for 7 days. Gingival crevicular fluid was collected from diseased and healthy sites at baseline and 3, 6, 12, and 24 months following treatment. Levels of 16 inflammatory/bone resorption markers were determined using Milliplex® . Univariate and correlation analyses were performed among all parameters/biomarkers. Discriminant analyses (DA) evaluated profile differences between LAP diseased and healthy sites at each time point as compared to the baseline. RESULTS: Reductions in the clinical parameters (except for visible plaque) were observed at all time points compared to the baseline. Levels of IL-12p70, IL-2, IL-6, MIP-1α, RANKL, and OPG were reduced after treatment, and several cytokines/chemokines were correlated with clinical parameters reductions. DA showed that differences in the immunoinflammatory profiles between LAP diseased and healthy sites decreased after periodontal treatment compared to the baseline. CONCLUSIONS: Periodontal treatment modified the local immunoinflammatory profile of LAP sites in the long term, as suggested by changes in biomarkers from baseline, along with clinical stability of the disease. (Clinicaltrials.gov number, NCT01330719).

Grade C molar-incisor pattern periodontitis subgingival microbial profile before and after treatment.

Aim: This study evaluated the influence of periodontal therapy on the microbiological profile of individuals with Grade C Molar-Incisor Pattern Periodontitis (C/MIP). Methods: Fifty-three African-American participants between the ages of 5-25, diagnosed with C/MIP were included. Patients underwent full mouth mechanical debridement with systemic antibiotics (metronidazole 250 mg + amoxicillin 500 mg, tid, 7 days). Subgingival samples were collected from a diseased and a healthy site from each individual prior to treatment and at 3, 6, 12, 18 and 24 months after therapy from the same sites. Samples were subjected to a 16S rRNA gene based-microarray. Results: Treatment was effective in reducing the main clinical parameters of disease. Aggregatibacter actinomycetemcomitans (A.a.) was the strongest species associated with diseased sites. Other species associated with diseased sites were Treponema lecithinolyticum and Tannerella forsythia. Species associated with healthy sites were Rothia dentocariosa/mucilaginosa, Eubacterium yurii, Parvimonas micra, Veillonella spp., Selenomonas spp., and Streptococcus spp. Overall, treatment was effective in strongly reducing A.a. and other key pathogens, as well as increasing health-associated species. These changes were maintained for at least 6 months. Conclusions:Treatment reduced putative disease-associated species, particularly A.a., and shifted the microbial profile to more closely resemble a healthy-site profile. (Clinicaltrials.gov registration #NCT01330719).

Dysregulation of genes and microRNAs in localized aggressive periodontitis.

AIM: Previous data from our laboratory have demonstrated that localized aggressive periodontitis (LAP) patients produce elevated levels of pro-inflammatory cytokines in response to TLR4 and TLR2 ligation compared to unrelated and periodontally healthy controls (HC). The aim of the present work is to evaluate the contribution of TLR-related gene expression and miRNA regulation in LAP disease. MATERIAL AND METHODS: Peripheral blood mononuclear cells (PBMCs) from LAP and health control (HC) patients were isolated. Gene and miRNA expression involved in TLR signalling pathway and immunopathology were evaluated in unstimulated PBMCs by real-time PCR (RT-PCR). RESULTS: TICAM-1 (TRIF), FOS, IRAK1, TLR2 and CCL2 genes and the miRNAs miR-9-5p, miR-155-5p and 203a-3p, miR-147a, miR-182-5p and miR-183-5p were significantly up-regulated in LAP compared to HC. CONCLUSIONS: Most of the genes and miRNAs overexpressed here are directly or indirectly related to immune response and inflammation. This profile supports our previous findings that suggests LAP patients have a "hyper-responsive" phenotype upon activation of TLR pathway by periodontal pathogens.

Association of P2RX7 functional variants with localized aggressive periodontitis.

OBJECTIVE: The purpose of this study was to investigate involvement of the P2X7 receptor in the rare condition, localized aggressive periodontitis. MATERIAL AND METHODS: Peripheral blood from 220 African Americans (103 with localized aggressive periodontitis and 117 healthy unrelated controls) was stimulated with lipopolysaccharide from E coli and Porphyromonas gingivalis. P2RX7 single nucleotide polymorphisms rs208294 (H155Y), rs1718119 (T348A), rs2230911 (T357S) and rs3751143 (E496A) were genotyped in 103 localized aggressive periodontitis patients and 117 healthy unrelated subjects. We examined genetic association between four P2RX7 single nucleotide polymorphisms and localized aggressive periodontitis, and tested for correlations between the single nucleotide polymorphisms and inflammatory response to lipopolysaccharide in blood samples from these patients. RESULTS: A significant association with localized aggressive periodontitis was observed with rs1718119 A (Thr) allele (P = 0.0063, odds ratio = 1.904) and with a haplotype containing this allele (P = 0.0075). Additionally, significant correlations with these data were found: the rs1718119 G allele correlated with greater production of IL-6, IL-2 and GM-CSF; the C (His) allele of rs208294 correlated with lower levels of IL-12p40; and the C (Thr) allele of rs2230911 correlated with greater levels of G-CSF. CONCLUSION: The data from these analyses support a possible biological relationship between P2RX7 genetic variants and inflammatory response in localized aggressive periodontitis patients.

Non-Surgical Therapy Reduces Presence of JP2 Clone in Localized Aggressive Periodontitis.

BACKGROUND: Previous studies have provided substantial evidence of the association of Aggregatibacter actinomycetemcomitans, and its highly leukotoxic JP2 genotype, with localized aggressive periodontitis (LAgP). The present study aims to evaluate presence of JP2 in individuals with LAgP after periodontal treatment. METHODS: Sixty African-American patients with LAgP, aged 5 to 25 years, were examined. At baseline, probing depth (PD), clinical attachment level (CAL), bleeding on probing, and plaque index were measured, and subgingival plaque was collected from LAgP diseased and healthy sites for each participant. Patients received whole-mouth ultrasonic debridement, scaling and root planing, and a 7-day prescription of amoxicillin and metronidazole. Participants were reevaluated and resampled and received regular maintenance therapy at 3, 6, and 12 months after treatment. Polymerase chain reaction was used to detect presence of the JP2 genotype before and after treatment. RESULTS: At baseline, the JP2 sequence was identified in 75% of LAgP diseased sites and in 56.67% of healthy sites. At 3, 6, and 12 months after treatment, the number of patients was 40, 31, and 31, respectively, and JP2 detection decreased to 17.5%, 6.45%, and 3.23%, respectively, in diseased sites (P <0.001) and to 2.5%, 3.23%, and 0%, respectively, in healthy sites (P <0.001). Clinical parameters of disease were also significantly reduced after therapy (P <0.001). Additionally, significant correlations were observed between JP2 presence and mean PD (P <0.002) and CAL (P <0.001), after therapy. CONCLUSION: Periodontal therapy was successful in reducing clinical parameters of LAgP and subgingival presence of JP2 in diseased and healthy sites.

Long-term clinical response to treatment and maintenance of localized aggressive periodontitis: a cohort study.

AIM: To evaluate long-term clinical response to periodontal therapy and maintenance in localized aggressive periodontitis (LAP). MATERIALS AND METHODS: One hundred forty-one African Americans diagnosed with LAP, aged 5-25 years, were enrolled. Patients underwent periodontal mechanical debridement plus 1 week of amoxicillin/metronidazole. Mechanical therapy was repeated as needed and clinical parameters were recorded at baseline, 3, 6, 12, 18 and 24 months, and two additional annual follow-up visits after treatment. Radiographs from primary dentition of patients with LAP in permanent dentition, and additional healthy siblings (HS) were analysed retrospectively. RESULTS: Periodontal therapy significantly improved probing depth and clinical attachment level up to 4 years (mean reductions: 2.18 ± 1.03 and 2.80 ± 1.43 mm, respectively). Percentage of affected sites was reduced at all time points and maintained up to 4 years. Non-compliance with antibiotics/appointments negatively affected the treatment response. Ninety per cent of LAP patients in permanent dentition and 32% of HS presented radiographic bone loss in primary dentition. CONCLUSIONS: Mechanical debridement with 1 week of systemic antibiotics along with proper periodontal maintenance was effective in the treatment and successful maintenance of LAP for up to 4 years. LAP in permanent dentition may be preceded in the primary dentition. Clinicaltrials.gov #NCT01330719.

Systemic inflammatory responses in patients with type 2 diabetes with chronic periodontitis.

OBJECTIVE: The objective of this case-control study was to quantify the immune responsiveness in individuals with type 2 diabetes (T2D) as compared with patients without diabetes (NT2D) diagnosed with periodontitis. RESEARCH DESIGN AND METHODS: Peripheral blood was collected from 20 patients with moderate-to-severe chronic periodontitis (10 T2D, 10 NT2D). Blood samples were stimulated with ultrapure Porphyromonas gingivalis and Escherichia coli lipopolysaccharide (LPS) for 24 hours. 14 cytokines/chemokines were quantified in culture supernatants using multiplex technology. RESULTS: T2D individuals demonstrated higher unstimulated levels of interleukin 6 (IL-6), IL-1ß, tumor necrosis factor α, interferon γ, IL-10, IL-8, macrophage inflammatory protein 1α (MIP1α), and 1ß (MIP1ß), and higher stimulated levels of IL-6, IL-8, IL-10, MIP1α and MIP1ß, along with lower unstimulated and stimulated levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) when compared with NT2D (p<0.05). Importantly, the LPS-induced levels of IL-6, IL-8, IL-10 and MIP1α strongly correlated with severity of disease, measured by pocket depths (PD), within the T2D group (r(2)≥0.7, p<0.05), but not within NT2D. CONCLUSIONS: Among patients with chronic periodontitis, patients with T2D seem to have an enhanced LPS-induced immune responsiveness than individuals without diabetes, which correlates with periodontal disease severity, concomitant with a less robust GM-CSF response. This data may in part explain the higher predisposition to periodontitis in this population.

Localized aggressive periodontitis immune response to healthy and diseased subgingival plaque.

AIM: The objective of this case-control study was to compare the inflammatory response of peripheral blood from localized aggressive periodontitis (LAP) patients when stimulated with healthy or diseased plaque samples. MATERIALS AND METHODS: Whole blood and subgingival plaque samples were collected from 13 LAP subjects, 14 siblings of LAP subjects and six periodontally healthy individuals. Whole blood was stimulated for 24 h with plaque samples generated from healthy or diseased sites. The levels of 14 cyto/chemokines were detected using multiplex technology. RESULTS: Localized aggressive periodontitis-derived cultures displayed higher levels of G-CSF, INFγ, IL10, IL12p40, IL1ß, IL-6, IL-8, MCP-1, MIP-1α, and TNFα, than control cultures regardless of stimulus used. Whole blood from healthy siblings displayed higher levels of IL-6 compared to control subjects, but lower levels than those observed in cultures from LAP participants. CONCLUSIONS: This study suggests that although bacteria is an important factor in eliciting the hyper-inflammatory response observed in LAP patients, the predisposition of host's response to bacterial presence may play a more significant role than the components of the stimulatory plaque.

Periodontal pathogens invade gingiva and aortic adventitia and elicit inflammasome activation in αvß6 integrin-deficient mice.

The American Heart Association supports an association between periodontal diseases and atherosclerosis but not a causal association. This study explores the use of the integrin ß6(-/-) mouse model to study the causality. We investigated the ability of a polymicrobial consortium of Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Fusobacterium nucleatum to colonize the periodontium and induce local and systemic inflammatory responses. Polymicrobially infected Itgß6(-/-) mice demonstrate greater susceptibility to gingival colonization/infection, with severe gingival inflammation, apical migration of the junctional epithelium, periodontal pocket formation, alveolar bone resorption, osteoclast activation, bacterial invasion of the gingiva, a greater propensity for the bacteria to disseminate hematogenously, and a strong splenic T cell cytokine response. Levels of atherosclerosis risk factors, including serum nitric oxide, oxidized low-density lipoprotein, serum amyloid A, and lipid peroxidation, were significantly altered by polybacterial infection, demonstrating an enhanced potential for atherosclerotic plaque progression. Aortic gene expression revealed significant alterations in specific Toll-like receptor (TLR) and nucleotide-binding domain- and leucine-rich-repeat-containing receptor (NLR) pathway genes in response to periodontal bacterial infection. Histomorphometry of the aorta demonstrated larger atherosclerotic plaques in Itgß6(-/-) mice than in wild-type (WT) mice but no significant difference in atherosclerotic plaque size between mice with polybacterial infection and mice with sham infection. Fluorescence in situ hybridization demonstrated active invasion of the aortic adventitial layer by P. gingivalis. Our observations suggest that polybacterial infection elicits distinct aortic TLR and inflammasome signaling and significantly increases local aortic oxidative stress. These results are the first to demonstrate the mechanism of the host aortic inflammatory response induced by polymicrobial infection with well-characterized periodontal pathogens.

Localized aggressive periodontitis treatment response in primary and permanent dentitions.

BACKGROUND: The comparative treatment response of children and young adults with localized aggressive periodontitis treatment (LAgP) affecting primary and permanent dentition is unknown. The objective of this study is to evaluate the influence of non-surgical periodontal therapy with adjunctive systemic antibiotics on the clinical outcome of children and young adults with primary versus permanent dentition affected by LAgP. METHODS: A cohort of 97 African American participants aged 5 to 21 years (30 males and 67 females; 22 primary and 75 permanent dentitions affected) diagnosed with LAgP were included. Patients presented with no significant medical history. All patients underwent periodontal therapy, which consisted of full-mouth mechanical debridement at baseline and the 3-, 6-, and 12-month appointments. Additionally, all patients were prescribed a 1-week regimen of systemic antibiotics at the initial appointment. Clinical parameters were analyzed, including probing depth, clinical attachment level (CAL), bleeding on probing, and percentage of visible plaque. RESULTS: Overall, periodontal therapy was found to be effective in improving the clinical outcomes of both primary and permanent dentitions. Although baseline CALs were similar between the groups, the reduction in mean CAL at 3, 6, and 12 months and reduction in percentage plaque at 3 months were significantly greater in primary dentition compared with permanent dentition. CONCLUSIONS: Non-surgical therapy with systemic antibiotics is effective for LAgP in both primary and permanent dentitions. A greater reduction in CAL in LAgP of primary dentition may suggest that younger children may carry a greater propensity for positive treatment outcomes and healing potential compared with children/young adults with permanent dentition.

Correlation of Aggregatibacter actinomycetemcomitans detection with clinical/immunoinflammatory profile of localized aggressive periodontitis using a 16S rRNA microarray method: a cross-sectional study.

OBJECTIVE: The objective of this study was to determine whether the detection of Aggregatibacter actinomycetemcomitans (Aa) correlates with the clinical and immunoinflammatory profile of Localized Aggressive Periodontitis (LAP), as determined by by 16S rRNA gene-based microarray. SUBJECTS AND METHODS: Subgingival plaque samples from the deepest diseased site of 30 LAP patients [PD ≥ 5 mm, BoP and bone loss] were analyzed by 16S rRNA gene-based microarrays. Gingival crevicular fluid (GCF) samples were analyzed for 14 cyto/chemokines. Peripheral blood was obtained and stimulated in vitro with P.gingivalis and E.coli to evaluate inflammatory response profiles. Plasma lipopolysaccharide (LPS) levels were also measured. RESULTS: Aa was detected in 56% of LAP patients and was shown to be an indicator for different bacterial community structures (p<0.01). Elevated levels of pro-inflammatory cyto/chemokines were detected in LPS-stimulated blood samples in both Aa-detected and Aa-non-detected groups (p>0.05). Clinical parameters and serum LPS levels were similar between groups. However, Aa-non-detected GCF contained higher concentration of IL-8 than Aa-detected sites (p<0.05). TNFα and IL1ß were elevated upon E.coli LPS stimulation of peripheral blood cells derived from patients with Aa-detected sites. CONCLUSIONS: Our findings demonstrate that the detection of Aa in LAP affected sites, did not correlate with clinical severity of the disease at the time of sampling in this cross-sectional study, although it did associate with lower local levels of IL-8, a different subgingival bacterial profile and elevated LPS-induced levels of TNFα and IL1ß.