Jean-Noel Vergnes

High-Fat Diet Induces Periodontitis in Mice through Lipopolysaccharides (LPS) Receptor Signaling: Protective Action of Estrogens

Background A fat-enriched diet favors the development of gram negative bacteria in the intestine which is linked to the occurrence of type 2 diabetes (T2D). Interestingly, some pathogenic gram negative bacteria are commonly associated with the development of periodontitis which, like T2D, is characterized by a chronic low-grade inflammation. Moreover, estrogens have been shown to regulate glucose homeostasis via an LPS receptor dependent immune-modulation. In this study, we evaluated whether diet-induced metabolic disease would favor the development of periodontitis in mice. In addition, the regulatory role of estrogens in this process was assessed. Methods Four-week-old C57BL6/J WT and CD14 (part of the TLR-4 machinery for LPS-recognition) knock-out female mice were ovariectomised and subcutaneously implanted with pellets releasing either placebo or 17β-estradiol (E2). Mice were then fed with either a normal chow or a high-fat diet for four weeks. The development of diabetes was monitored by an intraperitoneal glucose-tolerance test and plasma insulin concentration while periodontitis was assessed by identification of pathogens, quantification of periodontal soft tissue inflammation and alveolar bone loss. Results The fat-enriched diet increased the prevalence of periodontal pathogenic microbiota like Fusobacterium nucleatum and Prevotella intermedia, gingival inflammation and alveolar bone loss. E2 treatment prevented this effect and CD14 knock-out mice resisted high-fat diet-induced periodontal defects. Conclusions/Significance Our data show that mice fed with a diabetogenic diet developed defects and microflora of tooth supporting-tissues typically associated with periodontitis. Moreover, our results suggest a causal link between the activation of the LPS pathway on innate immunity by periodontal microbiota and HFD-induced periodontitis, a pathophysiological mechanism that could be targeted by estrogens.

Ethics in systematic reviews

Since its introduction by the Nuremberg Code and the Declaration of Helsinki, the place held by ethics in biomedical research has been continuously increasing in importance. The past 30 years have also seen exponential growth in the number of biomedical articles published. A systematic review of the literature is the scientific way of synthesising a plethora of information, by exhaustively searching out and objectively analysing the studies dealing with a given issue. However, the question of ethics in systematic reviews is rarely touched upon. This could lead to some drawbacks, as systematic reviews may contain studies with ethical insufficiencies, may be a possible way to publish unethical research and may also be prone to conflict of interest. Finally, informed consent given for an original study is not necessarily still valid at the systematic review level. There is no doubt that routine ethical assessment in systematic reviews would help to improve the ethical and methodological quality of studies in general. However, ethical issues change so much with time and location, and are so broad in scope and in context that it appears illusory to search for a universal, internationally accepted standard for ethical assessment in systematic reviews. Some simple suggestions could nevertheless be drawn from the present reflection and are discussed in the paper.

Concise Review: Mesenchymal Stromal Cells Used for Periodontal Regeneration: A Systematic Review

Periodontitis is a chronic infectious disease of the soft and hard tissues supporting the teeth. Recent advances in regenerative medicine and stem cell biology have paved the way for periodontal tissue engineering. Mesenchymal stromal cells (MSCs) delivered in situ to periodontal defects may exert their effects at multiple levels, including neovascularization, immunomodulation, and tissue regeneration. This systematic review had two goals: (a) to objectively quantify key elements for efficacy and safety of MSCs used for periodontal regeneration and (b) to identify patterns in the existing literature to explain differences between studies and suggest recommendations for future research. This systematic review provided good evidence of the capacity of MSCs to regenerate periodontal tissues in animals; however, experimentally generated defects used in animal studies do not sufficiently mimic the pathophysiology of periodontitis in humans. Moreover, the safety of such interventions in humans still needs to be studied. There were marked differences between experimental and control groups that may be influenced by characteristics that are crucial to address before translation to human clinical trials. We suggest that the appropriate combination of cell source, carrier type, and biomolecules, as well as the inclusion of critical path issues for a given clinical case, should be further explored and refined before transitioning to clinical trials. Future studies should investigate periodontal regenerative procedures in animal models, including rodents, in which the defects generated are designed to more accurately reflect the inflammatory status of the host and the shift in their pathogenic microflora.

Effect of periodontal treatment on the clinical parameters of patients with rheumatoid arthritis: study protocol of the randomized, controlled ESPERA trial

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory disorder that leads to joint damage, deformity, and pain. It affects approximately 1% of adults in developed countries. Periodontitis is a chronic oral infection, caused by inflammatory reactions to gram-negative anaerobic bacteria, and affecting about 35 to 50% of adults. If left untreated, periodontitis can lead to tooth loss. A significant association has been shown to exist between periodontitis and RA in observational studies. Some intervention studies have suggested that periodontal treatment can reduce serum inflammatory biomarkers such as C-reactive protein, or erythrocyte sedimentation rate. We hypothesize that periodontitis could be an aggravating factor in patients with RA, and that its treatment would improve RA outcomes. The aim of this clinical trial is to assess the effect of periodontal treatment on the biological and clinical parameters of patients with RA.Methods/designThe ESPERA (Experimental Study of Periodontitis and Rheumatoid Arthritis) study is an open-label, randomized, controlled trial. Subjects with both RA and periodontitis will be recruited at two university hospitals in southwestern France. In total, 40 subjects will be randomized into two arms (intervention and control groups), and will be followed up for 3 months. Intervention will consist of full-mouth supra-gingival and sub-gingival non-surgical scaling and root planing, followed by systemic antibiotic therapy, local antiseptics, and oral hygiene instructions. After the 3-month follow-up period, the same intervention will be applied to the subjects randomized to the control group.The primary outcome will be change of in Disease Activity Score in 28 Joints (DAS28) at the end of the follow-up period. Secondary outcomes will be the percentages of subjects with 20%, 50%, and 70% improvement in disease according to the American College of Rheumatology criteria. Health-related quality of life assessments (the Health Assessment Questionnaire and the Geriatric Oral Health Assessment Index) will also be compared between the two groups.DiscussionEvidence-based management of potential aggravating factors in subjects with active RA could be of clinical importance, yet there are few randomized controlled trials on the effect of periodontal treatment on the clinical parameters of RA. The ESPERA trial is designed to determine if non-surgical periodontal treatment could improve clinical outcomes in patients with active RA, and the quality of life of these patients.Trial registrationThe ESPERA Trial was registered in Current Controlled Trials [ISRCTN79186420] on 2012/03/20. The trial started recruiting on 2012/03/06.

Maternal dental caries and pre-term birth: results from the EPIPAP study.

Abstract Objective. The aim of this study was to analyse the association between maternal dental caries and pre-term birth (PTB), with a particular focus on the infection-suspected causes of pre-term births. Materials and methods. A secondary analysis was performed on data from the EPIPAP study, a French multi-centre case-control study. Cases were 1107 women giving birth to a singleton live-born infant before 37 weeks of gestation and controls were 1094 women delivering at 37 weeks or more. A sub-group of cases was defined as women with spontaneous labour and/or pre-term premature rupture of membranes (PPROM, n = 620). A full-mouth dental examination was performed after delivery. The main factor of interest was the presence of decay on at least one tooth. Results. Crude associations between presence of tooth decay and PTB or spontaneous PTB/PPROM were significant (OR = 1.21 [1.01–1.45] and OR = 1.25 [1.01–1.55], respectively). After adjustment for two sets of potential confounders (four pre-term birth risk factors and four social characteristics), for periodontitis status and for inter-examiner variability, tooth decay was not significantly associated with either PTB or spontaneous PTB/PPROM (aOR = 1.10 [0.91–1.32] and aOR = 1.14 [0.91–1.42], respectively). Conclusions. This study failed to demonstrate a significant association between tooth decay and pre-term birth. However, future well-designed studies are needed to further assess the link between dental caries and adverse pregnancy outcomes.

Oral health-related quality of life among outpatients with rheumatoid arthritis

OBJECTIVES The aims of the Oral Status And Rheumatoid Arthritis (OSARA) cross-sectional study were to study the oral health-related quality of life and to assess the associated factors in a population of outpatients with rheumatoid arthritis in France. METHODS The data were collected by five trained and standardised dentists who asked each subject the questions of a socio-demographic, behavioural and medical questionnaire, which was completed with the medical records, and performed the dental examination. Each subject filled out two self-assessment questionnaires: the Health Assessment Questionnaire and the General Oral Health Assessment Index. RESULTS Seventy-three subjects were included. The mean age of the participants was 60.2 ± 11.9 years and 75.3% were women. For 58.3% of the subjects, their self-perceived oral health-related quality of life was described as poor. The logistic regression analysis found that a small number of teeth and marked difficulties in dressing and grooming were associated with bad oral health-related quality of life [ORa = 10.5 (1.96-56.19) and ORa = 4.3 (1.15-15.77), respectively]. CONCLUSIONS More care should be given to the prevention of dental diseases in order to improve the oral health-related quality of life of patients with rheumatoid arthritis and their self-esteem, which will already be heavily affected.

Effect of fixed orthodontic appliances on salivary microbial parameters at 6 months: a controlled observational study

Objective The aim of this study was to assess the microbial changes in children with fixed orthodontic appliances compared with a control group of children without orthodontic treatment. Material and Methods Ninety-five children, aged between 12 and 16 years, participated in this study. Forty-eight subjects were fitted with fixed orthodontic appliances and forty-seven were free of any such appliances. The follow-up was 6 months for all children. The association between orthodontic appliances and high levels of Streptococcus mutans and Lactobacillus spp was assessed with logistic regression models, taking age, sex, pH and buffer capacity into account. Results Differences at baseline between the two groups were not statistically significant. We found that wearing a fixed orthodontic appliance was associated with high levels of Streptococcus mutans and Lactobacillus spp (adjusted OR: 6.65, 95% CI [1.98-22.37]; 9.49, 95% CI [2.57-35.07], respectively), independently of other variables. Conclusion The originality of the present epidemiological study was to evaluate the evolution of salivary microbial parameters in a population of children with fixed orthodontic appliances. Our results show an increase of Streptococcus mutans and Lactobacillus spp values during the follow-up. The whole dental workforce should be aware that preventive measures are of paramount importance during orthodontic treatment.

Cochrane systematic reviews in orthodontics

INTRODUCTION The Cochrane Collaboration is an international scientific not-for-profit organization the purpose of which is to produce and distribute systematic reviews of randomized clinical trials. The aim of this paper is to list the different existing Cochrane systematic reviews in the field of dentofacial orthopedics (DFO) and to analyse their main features. MATERIAL AND METHODS The choice of Cochrane systematic reviews based on dentofacial orthopedics was made from the exhaustive list published by the Cochrane Oral Health Group. RESULTS A total of 12 systematic Cochrane reviews related to dentofacial orthopedics were listed. All concluded on the need to conduct randomized clinical trials using more appropriate methodologies and comprising larger samples. None of these systematic reviews offered clear proof supporting any one form of treatment or treatment modality. DISCUSSION Despite the lack of relevant conclusions in the still meagre number of Cochrane systematic reviews related to DFO, it is essential for orthodontists to regularly consult the reviews in the framework of their daily evidence-based orthodontic practice. This is true too for orthodontic researchers as clinical DFO research needs to be extended with the setting up of methodologically unquestionable randomized clinical trials. However, there exist alternatives to randomized clinical trials offering a lower level of proof but which are better suited to the field of dentofacial orthopedics.

Discrete Distribution Based on Compound Sum to Model Dental Caries Count Data

Methods for analysing dental caries and associated risk indicators have evolved considerably in recent decades. The use of zero-inflated or hurdle models is increasing so as to take account of the decayed, missing, and filled teeth (DMFT) distribution, which is positively skewed and has a high proportion of zero scores. However, there is a need to develop new statistical models that involve pragmatic biological considerations on dental caries in epidemiological surveys. In this paper, we show that the zero-inflated and the hurdle models can both be expressed as a compound sum. Using the same compound sum, we then present the generalized negative binomial (GNB) distribution for dental caries count data, and provide a numerical application using the data of the EPIPAP study. The GNB model generates the best score functions while handling the lifetime dental caries disease process better. In conclusion, the GNB model suits the nature of some count data, in particular when structural zeros are unlikely to occur and when several latent spells can lead to new countable events. For these reasons, the use of the GNB distribution appears to be relevant for the modelling of dental caries count data.

Oral health and microbiota status in professional rugby players: A case-control study

OBJECTIVE Elite athletes are prone to develop oral diseases, which could increase the risk for injuries. The aim of this study was to evaluate the oral health and the composition of oral microbiota of elite rugby players compared to the general population. METHODS We set up a case-control study by screening 24 professional rugby players (PRG) and 22 control patients (CG) for dental and gingival examinations and performed a taxonomic analysis and a predicted functional analysis of oral microbiota. RESULTS The Decay, Missing and Filled (DMF) teeth index (5.54 ± 6.18 versus 2.14 ± 3.01; p = 0.01) and the frequency of gingivitis (58,33% versus 13.63%) were significantly increased in PRG compared to CG. PRG were characterized by a dysbiotic oral microbiota (Shannon Index: 3.32 ± 0.62 in PRG versus 3.79 ± 0.68 in CG; p = 0.03) with an increase of Streptococcus (58.43 ± 16.84 versus 42.60 ± 17.45; p = 0.005), the main genus implicated in caries. Predicted metagenomics of oral microbiota in rugby players was suggestive of a cariogenic metagenome favourable to the development of caries. CONCLUSIONS Our study shows that the oral health of PRG was poorer than the general population. PRG are characterized by a dysbiotic oral microbiota with an increase of the relative abundance of Streptococcus genus, positively correlated to the weight and negatively correlated to the diversity of oral microbiota. CLINICAL SIGNIFICANCE Dental screening should be included in the medical follow-up of professional rugby players as a part of their health management. New strategies such as using probiotics like Lactobacillus could help to control the dysbiosis of oral microbiota.