Clinical and Bacterial Markers of Periodontitis and Their Association with Incident All-Cause and Alzheimer's Disease Dementia in a Large National Survey.

Microbial agents including periodontal pathogens have recently appeared as important actors in Alzheimer's disease (AD) pathology. We examined associations of clinical periodontal and bacterial parameters with incident all-cause and AD dementia as well as AD mortality among US middle-aged and older adults. Clinical [Attachment Loss (AL); probing pocket depth (PPD)] and bacterial [pathogen immunoglobulin G (IgG)] periodontal markers were investigated in relation to AD and all-cause dementia incidence and to AD mortality, using data from the third National Health and Nutrition Examination Surveys (NHANES III, 1988-1994) linked longitudinally with National Death Index and Medicare data through January 1, 2014, with up to 26 years of follow-up. Sex- and age-specific multivariable-adjusted Cox proportional hazards models were conducted. Among those ≥65 years, AD incidence and mortality were consistently associated with PPD, two factors and one cluster comprised of IgG titers against Porphyromonas gingivalis (P. gingivalis), Prevotella melaninogenica (P. melaninogenica) and Campylobacter rectus (C. rectus) among others. Specifically, AD incidence was linked to a composite of C. rectus and P. gingivalis titers (per SD, aHR = 1.22; 95% CI, 1.04-1.43, p = 0.012), while AD mortality risk was increased with another composite (per SD, aHR = 1.46; 95% CI, 1.09-1.96, p = 0.017) loading highly on IgG for P. gingivalis, Prevotella intermedia, Prevotella nigrescens, Fusobacterium nucleatum, C. rectus, Streptococcus intermedius, Capnocylophaga Ochracea, and P. melaninogenica. This study provides evidence for an association between periodontal pathogens and AD, which was stronger for older adults. Effectiveness of periodontal pathogen treatment on reducing sequelae of neurodegeneration should be tested in randomized controlled trials.

Development of Oral Care Chip, a novel device for quantitative detection of the oral microbiota associated with periodontal disease.

Periodontal disease, the most prevalent infectious disease in the world, is caused by biofilms formed in periodontal pockets. No specific bacterial species that can cause periodontitis alone has been found in any study to date. Several periodontopathic bacteria are associated with the progress of periodontal disease. Consequently, it is hypothesized that dysbiosis of subgingival microbiota may be a cause of periodontal disease. This study aimed to investigate the relationship between the subgingival microbiota and the clinical status of periodontal pockets in a quantitative and clinically applicable way with the newly developed Oral Care Chip. The Oral Care Chip is a DNA microarray tool with improved quantitative performance, that can be used in combination with competitive PCR to quantitatively detect 17 species of subgingival bacteria. Cluster analysis based on the similarity of each bacterial quantity was performed on 204 subgingival plaque samples collected from periodontitis patients and healthy volunteers. A significant difference in the number of total bacteria, Treponema denticola, Campylobacter rectus, Fusobacterium nucleatum, and Streptococcus intermedia bacteria in any combination of the three clusters indicated that these bacteria gradually increased in number from the stage before the pocket depth deepened. Conversely, Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, and Streptococcus constellatus, which had significant differences only in limited clusters, were thought to increase in number as the pocket depth deepened, after periodontal pocket formation. Furthermore, in clusters where healthy or mild periodontal disease sites were classified, there was no statistically significant difference in pocket depth, but the number of bacteria gradually increased from the stage before the pocket depth increased. This means that quantitative changes in these bacteria can be a predictor of the progress of periodontal tissue destruction, and this novel microbiological test using the Oral Care Chip could be effective at detecting dysbiosis.

Frequency of putative periodontal pathogens among type 1 diabetes mellitus: a case-control study.

OBJECTIVE: The aim of the present study is to compare and assess the risk of periodontitis due to the presence of four putative periodontopathic bacteria viz., Eikenella corrodens, Campylobacter rectus, Prevotella intermedia and Prevotella nigrescens. To fulfil the above objective, polymerase Chain reaction using the primers targeting 16S rRNA gene of the bacterial species was performed with the subgingival plaque collected from the permanent first molars of type 1 diabetic children and age matched healthy children. RESULTS: The prevalence of periodontal pathogens in diabetic and healthy children was 6% and 16% for E. corrodens, 18% and 36% for C. rectus, 2% and 2% for P. intermedia, 4% and 0%, for P. nigrescens respectively. Statistically, significant difference was not observed for the prevalence of all the four periodontal pathogens between type 1 diabetic and healthy children (P = 1.00). The results of the present study thus reveal a negative correlation of type I diabetes to periodontitis in association to Eikenella corrodens, Campylobacter rectus, Prevotella intermedia and Prevotella nigrescens.

Unusual case of Lemierre's syndrome.

A young previously healthy patient presented with sepsis and cavitating pneumonia. Campylobacter rectus was isolated from blood cultures and subsequent CT neck showed an internal jugular vein thrombosis. Treatment was with antibiotics, anticoagulation and supportive management. Lemierre's syndrome is an infectious thrombophlebitis of the internal jugular vein. Although a rare diagnosis since the use of penicillin for treatment of acute pharyngitis, it is being reported with increasing frequency. Usually associated with Fusobacterium spp, we believe that this is the first reported case of Lemierre's caused by C. rectus-an anaerobic member of the human oral cavity flora, usually associated with localised periodontal disease. The bacillus was isolated from blood during the acute presentation.

Clival Osteomyelitis with Cavernous Sinus Thrombosis Due to Fusobacterium nucleatum and Campylobacter rectus Induced by Tooth Extraction.

A 70-year-old woman who had suffered from aseptic meningitis complained of chronic headache after dental treatment including tooth extraction. She developed a fever and respiratory failure. Based on chest computed tomography and head magnetic resonance imaging (MRI), she was diagnosed with osteomyelitis in the clivus accompanying moderate pituitary involvement, cavernous sinus thrombosis and septic pulmonary embolism. Both of the causal bacteria, Fusobacterium nucleatum and Campylobacter rectus, were isolated from her blood. Dual infection leading to clival osteomyelitis and cavernous sinus thrombosis has not been reported. It is important to perform enhanced MRI and blood culture for patients with chronic headache related to dental treatment.

Campylobacter rectus in the Oral Cavity Correlates with Proteinuria in Immunoglobulin A Nephropathy Patients.

BACKGROUND: Periodontitis-related pathogens, such as Campylobacter or Treponema species, have recently been shown to be associated with immunoglobulin A nephropathy (IgAN). Some strains of Streptococcus mutans, a major pathogen of dental caries, harbour the cnm gene that encodes a collagen-binding protein (Cnm). This has also been demonstrated to be associated with urinary protein levels in IgAN patients. OBJECTIVES: The purpose of the present study was to analyse the association of IgAN with C. rectus, Treponema denticola and cnm-positive S. mutans in the oral cavity of humans. METHODS: The presence of C. rectus, T. denticola and cnm-positive S. mutans strains in saliva samples of 117 IgAN patients and 56 healthy controls was evaluated by PCR, and the subjects' clinical parameters were analysed. RESULTS: C. rectus was significantly more prevalent in the IgAN group than in the control group (p < 0.05). The C. rectus-positive group was significantly associated with proteinuria in the IgAN group (p < 0.05). In addition, the C. rectus-positive and cnm-positive S. mutans group was shown to be more closely associated with urinary protein levels than the other groups (p < 0.0083). CONCLUSION: Our results suggest that harbouring C. rectus in the oral cavity could be associated with proteinuria in IgAN patients.

Fatal thoracic empyema involving Campylobacter rectus: A case report.

We report the case of a 69-year-old man admitted for septic shock secondary to necrotic pneumoniae complicated by thoracic empyema of fatal issue. Microbiological examination of pleural liquid revealed a mixed anaerobic flora involving Campylobacter rectus and Actinomyces meyeri. Campylobacter rectus is an infrequent anaerobic pathogen of oral origin To our knowledge, this is the first case report of fatal C. rectus - associated thoracic empyema, and only the second reported case in which identification was successfully performed by MALDI-TOF MS.

What is the Impact of Epstein-Barr Virus in Peri-implant Infection?

PURPOSE: To compare the qualitative and quantitative profile of Epstein-Barr virus (EBV) at external and internal implant surfaces between participants with peri-implantitis and healthy peri-implant tissues and to quantitatively assess the relation between EBV and periopathogens inside the microbiologic profile associated with peri-implantitis. MATERIALS AND METHODS: Microbiologic specimens were retrieved from 84 patients wearing 190 implants to estimate the levels of EBV and 10 periopathogens in the peri-implant pocket and internal-implant connection using quantitative polymerase chain reaction. RESULTS: The study sample consisted of 113 healthy and 77 peri-implantitis-affected implants. Statistical significance was not reached in EBV prevalence between peri-implantitis and healthy controls. EBV-positive participants demonstrated higher levels of Prevotella intermedia (Pi) and Campylobacter rectus (Cr) compared with EBV-negative participants. A positive correlation was demonstrated among EBV and Tannerella forsythia (Tf), Parvimonas micra (Pm), Fusobacterium nucleatum (Fn), and Cr levels in peri-implantitis-affected implants, while healthy controls demonstrated a positive correlation between EBV and Aggregatibacter actinomycetemcomitans (Aa), Pi, and Pm. CONCLUSION: EBV cannot be considered as a microbiologic marker of peri-implantitis. However, EBV could be considered as a risk factor and a peri-implantitis enhancer based on its positive correlations with pathogens associated with peri-implantitis.

Behavior of two Tannerella forsythia strains and their cell surface mutants in multispecies oral biofilms.

As a member of subgingival multispecies biofilms, Tannerella forsythia is commonly associated with periodontitis. The bacterium has a characteristic cell surface (S-) layer modified with a unique O-glycan. Both the S-layer and the O-glycan were analyzed in this study for their role in biofilm formation by employing an in vitro multispecies biofilm model mimicking the situation in the oral cavity. Different T. forsythia strains and mutants with characterized defects in cell surface composition were incorporated into the model, together with nine species of select oral bacteria. The influence of the T. forsythia S-layer and attached glycan on the bacterial composition of the biofilms was analyzed quantitatively using colony-forming unit counts and quantitative real-time polymerase chain reaction, as well as qualitatively by fluorescence in situ hybridization and confocal laser scanning microscopy. This revealed that changes in the T. forsythia cell surface did not affect the quantitative composition of the multispecies consortium, with the exception of Campylobacter rectus cell numbers. The localization of T. forsythia within the bacterial agglomeration varied depending on changes in the S-layer glycan, and this also affected its aggregation with Porphyromonas gingivalis. This suggests a selective role for the glycosylated T. forsythia S-layer in the positioning of this species within the biofilm, its co-localization with P. gingivalis, and the prevalence of C. rectus. These findings might translate into a potential role of T. forsythia cell surface structures in the virulence of this species when interacting with host tissues and the immune system, from within or beyond the biofilm.

Thoracic empyema caused by Campylobacter rectus.

We report a case of thoracic empyema caused by Campylobacter rectus, an organism considered as a periodontal pathogen but rarely recovered from extraoral specimens. The patient fully recovered through drainage of purulent pleural fluid and administration of antibiotics. The present case illustrates that C. rectus can be a cause of not only periodontal disease but also pulmonary infection.

Salivary Periodontopathic Bacteria in Children and Adolescents with Down Syndrome.

OBJECTIVE: To assess and compare salivary periodontopathic bacteria between groups of Down syndrome and non-Down syndrome children and adolescents. MATERIALS AND METHODS: This study included a sample of 30 Down syndrome children and adolescents (G-DS) and 30 age- and sex-matched non-Down syndrome subjects (G-ND). Clinical examination determined the gingival bleeding index (GBI) and plaque index. Unstimulated whole saliva samples were collected from all participants. The fluorescence in situ hybridization (FISH) technique identified the presence and density of eight periodontopathic bacteria in saliva. The statistical analysis included chi-square and Mann-Whitney U tests. RESULTS: In the G-DS group, bleeding on probing was more frequent (p = 0.037) and higher densities of Campylobacter rectus (p = 0.013), Porphyromonas gingivalis (p = 0.025), Treponema denticola (p = 0.026), Fusobacterium nucleatum (p = 0.013), Prevotella intermedia (p = 0.001) and Prevotella nigrescens (p = 0.008) were observed. Besides, in the G-DS, the densities of bacteria from the orange complex were significantly higher in the age group 3-7 years for F. nucleatum (p = 0.029), P. intermedia (p = 0.001) and P. nigrescens (p = 0.006). C. rectus was higher in the age group 8-12 years (p = 0.045). CONCLUSION: The results showed that children and adolescents with Down syndrome have higher susceptibility to periodontal disease and number of periodontopathic bacteria.

First report of severe acute otitis media caused by Campylobacter rectus and review of the literature.

Campylobacter rectus is a member of the human oral flora and is associated with periodontal disease. We report the first case of severe acute otitis media (AOM) due to C. rectus in a previous healthy 15-year-old boy, which was confirmed by 16S ribosomal RNA gene sequencing. C. rectus is a possible causative pathogen of AOM.

TLR4, NOD1 and NOD2 mediate immune recognition of putative newly identified periodontal pathogens.

Periodontitis is a polymicrobial inflammatory disease that results from the interaction between the oral microbiota and the host immunity. Although the innate immune response is important for disease initiation and progression, the innate immune receptors that recognize both classical and putative periodontal pathogens that elicit an immune response have not been elucidated. By using the Human Oral Microbe Identification Microarray (HOMIM), we identified multiple predominant oral bacterial species in human plaque biofilm that strongly associate with severe periodontitis. Ten of the identified species were evaluated in greater depth, six being classical pathogens and four putative novel pathogens. Using human peripheral blood monocytes (HPBM) and murine bone-marrow-derived macrophages (BMDM) from wild-type (WT) and Toll-like receptor (TLR)-specific and MyD88 knockouts (KOs), we demonstrated that heat-killed Campylobacter concisus, Campylobacter rectus, Selenomonas infelix, Porphyromonas endodontalis, Porphyromonas gingivalis, and Tannerella forsythia mediate high immunostimulatory activity. Campylobacter concisus, C. rectus, and S. infelix exhibited robust TLR4 stimulatory activity. Studies using mesothelial cells from WT and NOD1-specific KOs and NOD2-expressing human embryonic kidney cells demonstrated that Eubacterium saphenum, Eubacterium nodatum and Filifactor alocis exhibit robust NOD1 stimulatory activity, and that Porphyromonas endodontalis and Parvimonas micra have the highest NOD2 stimulatory activity. These studies allowed us to provide important evidence on newly identified putative pathogens in periodontal disease pathogenesis showing that these bacteria exhibit different immunostimulatory activity via TLR4, NOD1, and NOD2 (Clinicaltrials.gov NCT01154855).

Microbiologic and Clinical Findings of Implants in Healthy Condition and with Peri-Implantitis.

PURPOSE: To compare implants in healthy conditions and implants with peri-implantitis with regard to their clinical parameters and the microbiologic composition at the peri-implant sulcus, inside the implant connection, and the gingival sulcus of neighboring teeth. MATERIALS AND METHODS: A cross-sectional study was performed including consecutive patients with implants in healthy conditions and with peri-implantitis. Clinical parameters for which patients were screened included bleeding on probing, pocket depth, and plaque index at six sites. Samples for microbiologic analysis were obtained from three locations: the peri-implant sulcus, inside the implant connection, and the gingival sulcus of neighboring teeth. Quantitative real-time polymerase chain reaction (PCR) was carried out for total counts of 10 microorganisms: Aggregatibacter actinomycetemcomitans, Porphyromona gingivalis, Tanerella forsythia, Tanerella denticola, Prevotela intermedia, Peptostreptococcus micros, Fusobacterium nucleatum, Campylobacter rectus, Eikenella corrodens, and Candida albicans. The response variables were the percentage of positive sites and total bacterial counts. RESULTS: One hundred twenty-two implants in 57 patients were analyzed in the healthy group and 113 implants in 53 patients in the peri-implantitis group. Differences between the groups were statistically significant for bruxism, probing pocket depth, bleeding on probing, and radiographic bone level. Orange complex species (P intermedia, P micros, F nucleatum) were the most prevalent in the three types of sites for both groups, and prevalence values were higher in the peri-implantitis group. Differences in prevalence between groups were more marked inside the connection than in the peri-implant sulcus. Absolute loads of most microbes and total bacterial counts were higher for the peri-implantitis group in the three locations. Again, differences were bigger inside the connection than at the peri-implant sulcus. Significant interactions were found for prevalence and absolute microbial loads between groups and locations, and for the interaction of group × location. CONCLUSION: Clinical and microbiologic differences were observed between healthy subjects and those with peri-implantitis. Microbiologic differences between groups were more marked inside the connection than in the peri-implant sulcus. The potential role of the implant connection as a microbial reservoir for peri-implant diseases and in the outcome of their treatment should be confirmed with further studies.

Prevalence of eight putative periodontal pathogens in atherosclerotic plaque of coronary artery disease patients and comparing them with noncardiac subjects: A case-control study.

BACKGROUND: The study was aimed to assess the prevalence of periodontal pathogens namely Tannerella forsythia (T.f), Campylobacter rectus (C.r), Eikenella corrodens (E.c), Porphyromonas gingivalis (P.g), Treponema denticola (T.d), Prevotella nigrescens (P.n) ,Aggregatibacter actinomycetemcomitans (A.a), P.g (fi mA gene) and Prevotella intermedia (P.i), in the subgingival and the atheromatous plaque of patients with coronary artery disease (CAD), and comparing them with the noncardiac subjects thereby indicating the role of periodontal pathogenic bacteria in the progression of atherosclerosis in south Indian population. MATERIALS AND METHODS: 51 cardiac and non cardiac subjects within the age group of 40-80 years,who met the eligibility criteria, were selected and categorized as the experimental and control group respectively. Total number of teeth was recorded, and oral hygiene was evaluated using Plaque Index and Oral Hygiene Index (OHI). Periodontal pocket depth and clinical attachment level were also assessed as a part of periodontal examination. Subgingival plaque samples were collected with the help of with Gracey's curette in both the groups. In experimental group, biopsy was obtained from the atherosclerotic plaque during Coronary artery bypass grafting CABG procedure. Both, subgingival and the coronary atherosclerotic plaque samples were subjected to polymerase chain reaction (PCR) analysis for identification of the periodontal bacteria. STATISTICAL ANALYSIS: Mean, standard deviation and test of significance of quantitative variables such as periodontal parameters were compared between experimental group and control group. Kappa measures of agreement was done to analyze the relationship between the presence/absence of microorganisms in the subgingival and atherosclerotic plaque samples in the experimental group. RESULTS: The mean Plaque Index, Gingival Index, Russel's Periodontal Index, OHI, clinical attachment level, Pocket Depth Index was statistically significant in both the groups. Association of T.f, E.c, C.r, P.g, P.g (fi mA), T.d, P.i, P.n was significantly associated. A.a was absent in the control group, whereas only one patient in the experimental group was positive for the bacteria. Kappa analysis showed the significant association of periodontal bacteria T.f, C.r, P.g, P.g (fi mA), P.i and P.n in subgingival plaque and atherosclerotic plaque of the same patients of the experimental group. CONCLUSION: It is concluded that CAD subjects had higher prevalence of periodontal pathogens in subgingival biofilms as compared to the non cardiac subjects. Further, the number of bacteria was significantly associated between the subgingival and atherosclerotic plaques of the cardiac patients in south Indian population.

Bacterial profile of aggressive periodontitis in Morocco: a cross-sectional study.

BACKGROUND: Aggressive periodontitis (AgP) is one of the most severe forms of periodontal diseases. In Morocco, Aggregatibacter actinomycetemcomitans has been strongly associated with AgP, however limited knowledge is available about the implication of other periodontal pathogens in this entity. Therefore, the main aim of this study was to evaluate the composition of the subgingival microbiota in Moroccan patients with AgP. METHODS: Subgingival plaque samples were collected from 50 aggressive, 13 localized and 37 generalized periodontitis patients. Samples from 20 chronic periodontitis (ChP) patients were taken as controls. Samples collected from the four deepest periodontal pockets in each patient were pooled in pre-reduced transport fluid and examined by culture. RESULTS: A. actinomycetemcomitans was significantly more frequent (p = 0.004) in generalised AgP compared to ChP, and Porphyromonas gingivalis was less prevalent in localized AgP, when compared with generalized AgP (p = 0.040) or ChP (p = 0.016). Prevotella intermedia, Fusobacterium nucleatum and Tannerella forsythia were also frequently detected in all groups. Mean proportions of A. actinomycetemcomitans were significantly higher in AgP groups, when compared to ChP, and generalized AgP patients harbored significantly higher proportions of P. gingivalis and T. forsythia, when compared to localized AgP or ChP. CONCLUSIONS: A. actinomycetemcomitans, P. gingivalis, T. forsythia, P. intermedia and F. nucleatum were frequently detected in this Moroccan population with AgP. Differences in frequency of detection, counts and proportions of A. actinomycetemcomitans, P. gingivalis and T. forsythia suggests the presence of distinct microbiological profiles for localized AgP, generalized AgP and ChP patients.

Distribution of 8 periodontal microorganisms in family members of Chinese patients with aggressive periodontitis.

OBJECTIVE: To date, no information on the distribution of periodontal microorganisms among family members of Chinese patients with aggressive peridontitis (AgP) is available. The aim of the present study was to investigate the probability of transmission of eight periodontal microorganisms between patients with aggressive periodontitis and their family members. DESIGN: Saliva and pooled subgingival plaque samples were collected from 103 participants from 41 nuclear families (including 41 AgP probands, 19 mothers, 22 fathers, 21 siblings). Eight periodontal microorganisms, including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Campylobacter rectus, Prevotella intermedia, Prevotella nigrescens and Fusobacterium nucleatum were detected in these samples by the polymerase chain reaction (PCR). In addition, the distribution of fimA genotypes was assessed in P. gingivalis-positive individuals by PCR. RESULTS: P. gingivalis, T. forsythia, T. denticola, C. rectus and F. nucleatum were the most frequently detected species both in AgP probands and in their relatives. Kappa statistical analysis revealed that the detection of A. actinomycetemcomitans (Kappa = 0.503) and F. nucleatum (Kappa = 0.565) in probands was highly consistent with that in their relatives. Most probands shared the identical fimA genotype of P. gingivalis with their relatives. CONCLUSIONS: Our results suggested that the intrafamilial transmission of periodontal microorganisms may occur between Chinese patients with aggressive periodontitis and their relatives.

Evaluation of periodontal pathogens of the mandibular third molar pericoronitis by using real time PCR.

OBJECTIVES: The aim of this study was to investigate the mandibular third molar pericoronitis flora by using real-time polymerase chain reaction (PCR). MATERIALS AND METHODS: The quantitative values of Aggregatibacter actinomycetemcomitans (Aa), Campylobacter rectus (Cr), Fusobacterium nucleatum (Fn), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi) and Tannerella forsythia (Tf) were evaluated in comparison with the healthy third molar flora by using real time PCR. RESULTS: Aa, Cr, Pg, and Pi were not statistically significant but numerically higher than the pericoronitis group. In contrast to samples from control subjects, statistically significant higher numbers of Tf were detected in samples from pericoronitis patients. The study revealed the strong relation between risk of pericoronitis and the presence of Tf. Individuals who have Tf in their samples present with an almost eight times relative risk of pericoronitis as the individuals with an absence of Tf in their samples. CONCLUSION: Tf plays an important role in the development of clinical symptoms related to pericoronitis.