Metabolomics for dental caries diagnosis: Past, present, and future.

Dental caries, a prevalent global infectious condition affecting over 95% of adults, remains elusive in its precise etiology. Addressing the complex dynamics of caries demands a thorough exploration of taxonomic, potential, active, and encoded functions within the oral ecosystem. Metabolomic profiling emerges as a crucial tool, offering immediate insights into microecosystem physiology and linking directly to the phenotype. Identified metabolites, indicative of caries status, play a pivotal role in unraveling the metabolic processes underlying the disease. Despite challenges in metabolite variability, the use of metabolomics, particularly via mass spectrometry and nuclear magnetic resonance spectroscopy, holds promise in caries research. This review comprehensively examines metabolomics in caries prevention, diagnosis, and treatment, highlighting distinct metabolite expression patterns and their associations with disease-related bacterial communities. Pioneering in approach, it integrates singular and combinatory metabolomics methodologies, diverse biofluids, and study designs, critically evaluating prior limitations while offering expert insights for future investigations. By synthesizing existing knowledge, this review significantly advances our comprehension of caries, providing a foundation for improved prevention and treatment strategies.

Dental Caries, Race and Incident Ischemic Stroke, Coronary Heart Disease, and Death.

BACKGROUND: Dental caries is a highly prevalent disease worldwide. In the United States, untreated dental caries is present in >1 in 5 adults. The objective of this study was to determine the relationship between dental caries and incident ischemic stroke, coronary heart disease (CHD) events, and death. METHODS: The dental cohort (n=6351) of the ARIC study (Atherosclerosis Risk in Communities) was followed for incident ischemic stroke, CHD event, and all-cause mortality. Of all the participants at visit 4 (n=11 656), those who were unable to go through dental examination, or with prevalent ischemic stroke and CHD events, were excluded. The full-mouth dental examination was conducted at visit 4 (1996-1998), assessing dental caries. The dose response of decayed, missing, and filled surfaces due to caries was assessed and related to the outcome. Outcomes were assessed through the end of 2019. Additionally, the effect of regular dental care utilization on dental caries was evaluated. RESULTS: Participants with ≥1 dental caries had an increased risk of stroke (adjusted hazard ratio [HR], 1.40 [95% CI, 1.10-1.79]) and death (adjusted HR, 1.13 [95% CI, 1.01-1.26]) but not for CHD events (adjusted HR, 1.13 [95% CI, 0.93-1.37]). The association of dental caries and ischemic incident stroke was significantly higher in the African American population compared with the White subgroup (interaction term P=0.0001). Increasing decayed, missing, and filled surfaces were significantly associated with stroke (adjusted HR, 1.006 [95% CI, 1.001-1.011]) and death (adjusted HR, 1.003 [95% CI, 1.001-1.005]) but not CHD (adjusted HR, 1.002 [95% CI, 1.000-1.005]). Regular dental care utilization lowered (adjusted odds ratio, 0.19 [95% CI, 0.16-0.22]; P<0.001) the chance of caries. CONCLUSIONS: Among the cohort, dental caries was independently associated with the risk of ischemic stroke and death, with the effect higher in African American participants. Regular dental care utilization was associated with a lower chance of caries, emphasizing its relevance in the prevention of these events.

Salivary Diagnosis of Dental Caries: A Systematic Review.

The activity of dental caries, combined with its multifactorial etiology, alters salivary molecule composition. The present systematic review was developed to answer the following question: "Are salivary biomarkers reliable for diagnosis of dental caries?". Following the "Preferred Reporting Item for Systematic Reviews and Meta-analysis" (PRISMA) guidelines, the review was conducted using multiple database research (Medline, Web of Science, and Scopus). Studies performed on healthy subjects with and without dental caries and providing detailed information concerning the clinical diagnosis of caries (Decayed, Missing, Filled Teeth-DMFT and International Caries Detection and Assessment System-ICDAS criteria) were included. The quality assessment was performed following a modified version of the Joanna Briggs Institute Prevalence Critical Appraisal Checklist. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, ID: CRD42022304505). Sixteen papers were included in the review. All studies reported statistically significant differences in the concentration of salivary molecules between subjects with and without caries (p < 0.05). Proteins were the most investigated molecules, in particular alpha-amylase and mucins. Some studies present a risk of bias, such as identifying confounding factors and clearly defining the source population. Nevertheless, the 16 papers were judged to be of moderate to high quality. There is evidence that some salivary compounds studied in this review could play an important diagnostic role for dental caries, such as salivary mucins, glycoproteins (sCD14), interleukins (IL-2RA, 4,-13), urease, carbonic anhydrase VI, and urea.

Plant-Derived Compounds: A Promising Tool for Dental Caries Prevention.

There is a growing shift from the use of conventional pharmaceutical oral care products to the use of herbal extracts and traditional remedies in dental caries prevention. This is attributed to the potential environmental and health implications of contemporary oral products. This comprehensive review aims at the analysis of plant-derived compounds as preventive modalities in dental caries research. It focuses on data collected from 2019 until recently, trying to emphasize current trends in this topic. The research findings suggest that several plant-derived compounds, either aqueous or ethanolic, exhibit notable antibacterial effects against Streptococcus mutans and other bacteria related to dental caries, with some extracts demonstrating an efficacy comparable to that of chlorhexidine. Furthermore, in vivo studies using plant-derived compounds incorporated in food derivatives, such as lollipops, have shown promising results by significantly reducing Streptococcus mutans in high-risk caries children. In vitro studies on plant-derived compounds have revealed bactericidal and bacteriostatic activity against S. mutans, suggesting their potential use as dental caries preventive agents. Medicinal plants, plant-derived phytochemicals, essential oils, and other food compounds have exhibited promising antimicrobial activity against oral pathogens, either by their anti-adhesion activity, the inhibition of extracellular microbial enzymes, or their direct action on microbial species and acid production. However, further research is needed to assess their antimicrobial activity and to evaluate the cytotoxicity and safety profiles of these plant-derived compounds before their widespread clinical use can be recommended.

Metabolomics reveals high fructose-1,6-bisphosphate from fluoride-resistant Streptococcus mutans.

BACKGROUND: Fluoride-resistant Streptococcus mutans (S. mutans) strains have developed due to the wide use of fluoride in dental caries prevention. However, the metabolomics of fluoride-resistant S. mutans remains unclear. OBJECTIVE: This study aimed to identify metabolites that discriminate fluoride-resistant from wild-type S. mutans. MATERIALS AND METHODS: Cell supernatants from fluoride-resistant and wild-type S. mutans were collected and analyzed by liquid chromatography-mass spectrometry. Principal components analysis and partial least-squares discriminant analysis were performed for the statistical analysis by variable influence on projection (VIP > 2.0) and p value (Mann-Whitney test, p < 0.05). Metabolites were assessed qualitatively using the Human Metabolome Database version 2.0 ( http://www.hmdb.ca ), or Kyoto Encyclopedia of Genes and Genomes ( http://www.kegg.jp ), and Metaboanalyst 6.0 ( https://www.metaboanalyst.ca ). RESULTS: Fourteen metabolites differed significantly between fluoride-resistant and wild-type strains in the early log phase. Among these metabolites, 5 were identified. There were 32 differential metabolites between the two strains in the stationary phase, 13 of which were identified. The pyrimidine metabolism for S. mutans FR was matched with the metabolic pathway. CONCLUSIONS: The fructose-1,6-bisphosphate concentration increased in fluoride-resistant strains under acidic conditions, suggesting enhanced acidogenicity and acid tolerance. This metabolite may be a promising target for elucidating the cariogenic and fluoride resistant mechanisms of S. mutans.

The complement system as a key modulator of the oral microbiome in health and disease.

In this review, we address the interplay between the complement system and host microbiomes in health and disease, focussing on oral bacteria known to contribute to homeostasis or to promote dysbiosis associated with dental caries and periodontal diseases. Host proteins modulating complement activities in the oral environment and expression profiles of complement proteins in oral tissues were described. In addition, we highlight a sub-set of bacterial proteins involved in complement evasion and/or dysregulation previously characterized in pathogenic species (or strains), but further conserved among prototypical commensal species of the oral microbiome. Potential roles of these proteins in host-microbiome homeostasis and in the emergence of commensal strain lineages with increased virulence were also addressed. Finally, we provide examples of how commensal bacteria might exploit the complement system in competitive or cooperative interactions within the complex microbial communities of oral biofilms. These issues highlight the need for studies investigating the effects of the complement system on bacterial behaviour and competitiveness during their complex interactions within oral and extra-oral host sites.

Competitive dynamics and balance between Streptococcus mutans and commensal streptococci in oral microecology.

Dental caries, as a biofilm-related disease, is closely linked to dysbiosis in microbial ecology within dental biofilms. Beyond its impact on oral health, bacteria within the oral cavity pose systemic health risks by potentially entering the bloodstream, thereby increasing susceptibility to bacterial endocarditis, among other related diseases. Streptococcus mutans, a principal cariogenic bacterium, possesses virulence factors crucial to the pathogenesis of dental caries. Its ability to adhere to tooth surfaces, produce glucans for biofilm formation, and metabolize sugars into lactic acid contributes to enamel demineralization and the initiation of carious lesions. Its aciduricity and ability to produce bacteriocins enable a competitive advantage, allowing it to thrive in acidic environments and dominate in changing oral microenvironments. In contrast, commensal streptococci, such as Streptococcus sanguinis, Streptococcus gordonii, and Streptococcus salivarius, act as primary colonizers and compete with S. mutans for adherence sites and nutrients during biofilm formation. This competition involves the production of alkali, peroxides, and antibacterial substances, thereby inhibiting S. mutans growth and maintaining microbial balance. This dynamic interaction influences the balance of oral microbiota, with disruptions leading to shifts in microbial composition that are marked by rapid increases in S. mutans abundance, contributing to the onset of dental caries. Thus, understanding the dynamic interactions between commensal and pathogenic bacteria in oral microecology is important for developing effective strategies to promote oral health and prevent dental caries. This review highlights the roles and competitive interactions of commensal bacteria and S. mutans in oral microecology, emphasizing the importance of maintaining oral microbial balance for health, and discusses the pathological implications of perturbations in this balance.

Comparative evaluation of anti-biofilm and anti- adherence potential of plant extracts against Streptococcus mutans: A therapeutic approach for oral health.

Dental caries predominantly attributed to the cariogenic nature of Streptococcus mutans, continue to pose a substantial global challenge to oral health. In response to this challenge, this study aimed to evaluate the effectiveness of leaf extracts (LEs) and essential oils (EOs) derived from different medicinal plants in inhibiting the growth of Streptococcus mutans biofilm. In vitro and in silico approaches were employed to identify active compounds and assess their inhibitory effects on S. mutans. Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were measured to determine the anti-biofilm and anti-adherence activity against S. mutans. Biofilm viability (CFU/mL) and extracellular polymeric substance (EPS) concentration were quantified. GC-MS analysis was utilized to identify active compounds in the most effective plant extracts exhibiting anti-S. mutans activity. A high-throughput screening focused on the interaction between these compounds and the target enzyme SortaseA (SrtA) using molecular docking was performed. Results indicated that Cymbopogon citratus displayed the highest efficacy in reducing S. mutans biofilm formation and adhesion activity, achieving 90 % inhibition at an MIC value of 12 µg/mL. Among the 12 bioactive compounds identified, trans-Carvyl acetate exhibited the lowest binding energy with SrtA (-6.0 Kcal/mole). Trans-Carvyl acetate also displayed favorable pharmacokinetic properties. This study provides novel insights into the anti-S. mutans properties of C. citratus and suggests its potential as a therapeutic approach for oral health. Further research is needed to explore the combined effect of plant extracts for enhanced protection against dental caries.

Interplay between dental caries pathogens, periodontal pathogens, and sugar molecules: approaches for prevention and treatment.

Globally, oral diseases affect nearly 3.5 billion people, accounting for 4.6% of the healthcare expenditure. Common oral diseases include dental caries and periodontal disease, associated with biofilms formed by cariogenic pathogens. Epidemiological studies associate carbohydrates with these diseases due to  the sugars metabolized by cariogenic pathogens. This review focuses on dental caries and periodontal pathogens, quorum sensing, lectin-carbohydrate interactions, and various sugar molecules. Cariogenic sugars significantly influence biofilms by enhancing pathogen adhesion, viability, and gene expressions associated with biofilm formation. Moreover, lectin-carbohydrate interactions contribute to biofilm stability. Disrupting these interactions is a potential strategy for oral disease prevention. The use of nanoparticles, such as quantum dots, provides novel insights into lectin-sugar interactions and the development of inhibitors. Additionally, nanomaterials like calcium phosphate nanoparticles neutralize acids and inhibit microbial growth. This overview emphasizes understanding the relationships between oral diseases, microbial communities, and sugars to devise preventive and therapeutic strategies against oral diseases.

Dental Caries a Risk Factor for Intracerebral Hemorrhage.

INTRODUCTION: Streptococcus mutans is a known cause of dental caries that contains a collagen-binding protein, Cnm, and exhibits inhibition of platelet aggregation and matrix metalloproteinase-9 activation. This strain has been linked to aggravation of experimental intracerebral hemorrhage (ICH) and may be a risk factor for ICH. The purpose of this study was to test the association between dental caries and incident ICH. METHODS: The presence of dental caries and periodontal disease was assessed in subjects from the Dental Atherosclerosis Risk in Communities (DARIC) study without prior stroke or ICH. This cohort was followed for incident ICH over a period of 10 years. Cox regression was used to compute crude and adjusted hazards ratio from the dental assessment. RESULTS: Among 6,315 subjects, dental surface caries and/or root caries were recorded in 1,338 (27%) subjects. Of those, 7 (0.5%) had incident ICH over a period of 10 years following the visit 4 assessment. Of the remaining 4,977 subjects, 10 (0.2%) had incident ICH. Those with dental caries versus those without dental caries were slightly younger (mean age 62.0 ± 5.7 vs. 62.4 ± 5.6, p = 0.012), had a greater proportion of males (51 vs. 44%, p < 0.001), African Americans (44 vs. 10%, p < 0.001), and were hypertensive (42 vs. 31%, p < 0.001). The association between caries and ICH was significant (crude HR 2.69, 95% CI 1.02-7.06) and strengthened after adjustment for age, gender, race, education level, hypertension, and periodontal disease (adjusted HR 3.88, 95% CI 1.34-11.24). CONCLUSION: Dental caries is a potential risk for incident ICH after caries detection. Future studies are needed to determine if treatment of dental caries can reduce the risk of ICH.

Bayesian modeling of spatially differentiated multivariate enamel defects of the children's primary maxillary central incisor teeth.

BACKGROUND: The analysis of dental caries has been a major focus of recent work on modeling dental defect data. While a dental caries focus is of major importance in dental research, the examination of developmental defects which could also contribute at an early stage of dental caries formation, is also of potential interest. This paper proposes a set of methods which address the appearance of different combinations of defects across different tooth regions. In our modeling we assess the linkages between tooth region development and both the type of defect and associations with etiological predictors of the defects which could be influential at different times during the tooth crown development. METHODS: We develop different hierarchical model formulations under the Bayesian paradigm to assess exposures during primary central incisor (PMCI) tooth development and PMCI defects. We evaluate the Bayesian hierarchical models under various simulation scenarios to compare their performance with both simulated dental defect data and real data from a motivating application. RESULTS: The proposed model provides inference on identifying a subset of etiological predictors of an individual defect accounting for the correlation between tooth regions and on identifying a subset of etiological predictors for the joint effect of defects. Furthermore, the model provides inference on the correlation between the regions of the teeth as well as between the joint effect of the developmental enamel defects and dental caries. Simulation results show that the proposed model consistently yields steady inferences in identifying etiological biomarkers associated with the outcome of localized developmental enamel defects and dental caries under varying simulation scenarios as deemed by small mean square error (MSE) when comparing the simulation results to real application results. CONCLUSION: We evaluate the proposed model under varying simulation scenarios to develop a model for multivariate dental defects and dental caries assuming a flexible covariance structure that can handle regional and joint effects. The proposed model shed new light on methods for capturing inclusive predictors in different multivariate joint models under the same covariance structure and provides a natural extension to a nested hierarchical model.

Diet-derived circulating antioxidants, periodontitis and dental caries: A Mendelian randomization study.

BACKGROUND AND OBJECTIVE: Given the potential association between oxidative stress, periodontitis and dental caries, whether dietary supplementation with antioxidants is beneficial for periodontitis and dental caries has been widely reported, but remains controversial. This study aims to clarify these relationships through two-sample Mendelian randomization (MR) analysis. METHODS: Circulating antioxidants (copper, selenium, zinc, ascorbate, ß-carotene, lycopene, retinol and vitamin E) were derived from absolute circulating antioxidants and circulating antioxidant metabolites. Summary data of periodontitis and dental caries were obtained from two separate databases, respectively. We performed inverse-variance weighted (IVW) analysis separately in different databases, followed by meta-analysis. The robustness of results was examined by sensitivity analyses, including three complementary MR methods, heterogeneity and pleiotropy tests, and PhenoScanner query. RESULTS: IVW analysis showed that elevated levels of absolute circulating retinol reduced the risk of periodontitis (GLIDE: OR = 0.41, 95% CI = 0.18-0.95, p = .038, power = 100%; FinnGen: OR = 0.15, 95% CI = 0.04-0.54, p = .004, power = 100%). The pooled OR for periodontitis risk per unit increase of retinol is 0.30 (95% CI = 0.15-0.61, p = .001, I2 = 40.3%, power = 100%). No significant associations were noted for genetically predicted circulating antioxidants and dental caries risk. The sensitivity analyses yielded similar estimates. CONCLUSION: This study demonstrates that a negative causality between circulating retinol and periodontitis risk, and null linkage between circulating antioxidants and dental caries risk, suggesting potential strategies for the prevention and control of periodontitis.

The association between dental caries and steroid-sensitive nephrotic syndrome in children.

BACKGROUND: Pathogenesis and relapse of steroid-sensitive nephrotic syndrome (SSNS) are primarily associated with infection. Dental caries is the most common chronic progressive oral infection in children. However, clinical studies of SSNS combined with dental caries in children are rare. METHODS: In our retrospective cohort study from January 2021 to June 2022, 145 children with SSNS were included in the baseline analysis and 105 in the follow-up analysis. The follow-up period was 1 year. The primary study endpoints were the relapse-free period and frequently relapsing nephrotic syndrome (FRNS). Secondary endpoints included the number and triggers of relapses and concomitant medications. RESULTS: The median age was 5.5 years, with a caries rate of 60.7%, the mean DMFT/dmft was 3.86, and the caries filling rate was 1.6%. Except for the lower proportion of high household income and high parental education observed in the caries group, no statistical differences were found when comparing the other baseline data with the non-caries group. The caries group had a shorter relapse-free period and a lower 1-year cumulative relapse-free survival rate (HR = 1.90, 95% CI 1.17-3.09, P = 0.009). Univariate regression analysis showed caries associated with FRNS (OR = 2.714, 95% CI 1.021-7.219, P = 0.045), but the correlation no longer remained in the multivariate analysis. Additionally, seven cases of caries-derived pulpal periapical inflammation triggered SSNS relapses. The caries group had more infection triggers and concomitant medication use. CONCLUSION: Dental caries and relapse of SSNS are potentially associated, but careful evaluation is needed.

Antineoplastic therapy is an independent risk factor for dental caries in childhood cancer patients: a retrospective cohort study.

PURPOSE: To evaluate the antineoplastic therapy (AT) as a risk factor for dental caries lesions independent of other risk factors such as income, family education, stimulated salivary flow rate, hygiene habits, frequency of sugar intake, and microbiota in childhood cancer (CC) patients. METHODS: 72 individuals were divided into CC patients (n=36) and healthy individuals (control group - CT n=36). Demographic data, hygiene habits, frequency of sugar intake, CC type, and AT were collected. Stimulated salivary flow rate was measured and the presence and concentration of Streptococcus mutans were assessed using a real-time polymerase chain reaction (qPCR) technique. Clinical evaluations included plaque index (PI) and decayed-missing-filled-teeth index (dmft/DMFT). Descriptive statistics, T-test, Mann-Whitney test, chi-square test, Fisher's exact test, and two-way analysis of variance were used for data analysis (p<0.05). RESULTS: At the time of oral evaluation, both groups exhibited similar ages with means of 12.0±3.9 years old for CC and 12.0±4.0 years old for CT patients. All CC patients underwent chemotherapy with nine also undergoing radiotherapy. Significant differences were observed between the groups in terms of color/race, income, family education, and hygiene habits. However, no statistically significant differences were found between groups regarding the frequency of sugar intake, stimulated salivary flow rate, or the concentration of Streptococcus mutans (qPCR technique). For clinical parameters, the DMF (CC:1.80, CT: 0.75), decayed (CC: 0.88, CT: 0.19), missing (CC: 0.25, CT:0), and PI (CC: 30.5%, CT: 22.6%) were higher in the CC group (p<0.05). CONCLUSION: Childhood cancer (CC) patients undergoing antineoplastic therapy (AT) exhibit a higher prevalence of dental caries, regardless of income/education, frequency of sugar intake, stimulated salivary flow rate, and microbiota.

Radiation-induced xerostomia and cariogenic dietary habits.

PURPOSE: Despite the availability of various prevention methods, dental caries continue to be diagnosed in patients receiving head and neck radiotherapy (RT). Since conventional approaches do not evaluate posttreatment alterations in dietary behaviors, we aimed to assess the influence of radiation-induced xerostomia on post-RT cariogenic dietary habits in patients. METHODS: Fifty-seven patients completed the Xerostomia Questionnaire (XQ) and answered questions regarding daily cariogenic food and beverage (CFB) intake, daily tooth brushing, fluoride application, and subjective total taste acuity (STTA). They also underwent evaluations to determine the Simplified Oral Hygiene Index (OHI-S) score, Saxon test score, number of decayed-missing-filled teeth (DMFT), and proportion of DMFT to the test teeth (DMFT rate). Clinical records were searched for information regarding RT modalities, including the median of the mean dose to the parotid glands, days after the completion of RT, submandibular gland resection, whole-neck irradiation, and the DMFT value and rate before RT. The patients were divided into low and high XQ score groups based on the median XQ score of 47.5 for the two sample tests. Univariable and multivariable regression analyses were used to identify independent factors for frequent CFB intake. RESULTS: Higher XQ scores were associated with a significantly greater frequency of CFB intake (p = 0.028*). Regression analysis also identified a higher XQ score (p = 0.017*) as an independent risk factor for frequent CFB intake. CONCLUSION: Radiation-induced xerostomia increased the frequency of CFB intake.

Preventive and restorative alternatives to caries by irradiation: a scoping review.

PURPOSE: This study is to conduct a comprehensive scoping review to map scientific evidence and clarify concepts regarding the commonly recommended preventive and restorative dental treatments for patients diagnosed with head and neck cancer (HNC) and subjected to radiotherapy. MATERIAL AND METHODS: This systematic scoping review was performed under the PRISMA-ScR guidelines. The study's experimental design was registered in the Open Science Framework. In vitro studies that evaluated preventive and restorative dental treatment over 50 Gy radiation doses were included. The search was conducted in November 2023 in five electronic databases (PubMed, Scopus, Web of Science, Cochrane Library, and Embase) without language or date restriction. A search strategy was applied based on keywords, MeSh terms, or synonyms. A descriptive analysis was conducted. RESULTS: A total of 49 studies, out of 3679 original articles identified, were included and reviewed. Of the included studies, three evaluated saliva stimulants and 35 evaluated fluoride-based preventive materials: gel (n = 18) toothpaste (n = 11) mouth rinse (n = 8) and varnish (n = 5) while 14 evaluated restorative materials: resin composite (n = 12) glass ionomer cement (n = 6) and amalgam (n = 1) Of those studies, 36 were clinical trials and 13 were in vitro studies. CONCLUSION: Fluoride gel was the most frequently recommended preventive material for preventing radiation caries with supportive clinical evidence. Resin composite and glass ionomer were the most frequently used restorative materials, respectively. However, there is not yet clinical evidence to support the use of resin composite in irradiated teeth.

Are periodontitis and dental caries associated? A systematic review with meta-analyses.

AIM: The epidemiological relationship between periodontitis and caries remains controversial, and evidence synthesis is currently lacking. Therefore, this systematic review was designed to answer the following PECO question: 'In human adults (P), do subjects suffering from periodontitis (E) have higher presence/number of untreated carious lesions and caries experience (O) than subjects not suffering from periodontitis (C)?'. MATERIALS AND METHODS: Observational studies that met specific inclusion criteria established to answer to the PECO question were included. Two review authors independently searched for eligible studies, screened the titles and abstracts, carried out the full text analysis, extracted the data and performed the risk of bias assessment. In case of disagreement, a third review author took the final decision during ad hoc consensus meetings. Data synthesis was carried out through random-effects meta-analyses. RESULTS: A total of 18 studies on 21 cohorts, involving 135,018 participants, were included. Meta-analyses showed a significant association between periodontitis and the presence of at least one tooth with either untreated carious lesions (odds ratio [OR] = 1.63; 95% confidence interval [CI]: 1.32-2.01; p <.00; I2 = 83.0%) or caries experience (decayed and filled teeth ≥ 1) (OR = 1.27; 95% CI: 1.01-1.59; p = .038; I2 = 90.0%). Moreover, subjects with periodontitis exhibited a higher number of surfaces (difference in means [MD] = 0.86; 95% CI: 0.46-1.27; p <.001; I2 = 0.0%) and teeth (MD = 0.35; 95% CI: 0.28-0.42; p <.001; I2 = 69.6%) with untreated carious lesions, as well as a higher number of teeth with caries experience (standardized difference in means [SMD] = 1.46; 95% CI: 0.15-2.78; p = .029; I2 = 98.9%) compared with those without periodontitis. Sensitivity analyses focusing on severe periodontitis as exposure mostly showed consistent results. Estimates for caries experience were only slightly attenuated in adjusted models compared with crude models. Subgroup analyses by caries location also indicated that periodontitis was associated only with root caries, while it was not with caries affecting the anatomical crown. CONCLUSIONS: Periodontitis was found to be associated with the presence and number of treated/untreated root carious lesions. Therefore, caries-specific preventive measures (e.g., fluorides) should be considered for individuals with periodontitis.

Pathway analysis between dental caries and oral health-related quality of life in the transition from childhood to adolescence: a 10-year cohort study.

PURPOSE: To evaluate the direct and indirect pathways between cavitated carious lesions and oral health-related quality of life (OHRQoL) during the transition from childhood to adolescence. METHODS: A prospective cohort study followed an initial sample of 639 children (one to five years old), in southern Brazil for ten years. In addition to the baseline (T1), two subsequent reassessments were conducted after seven (T2) and ten years (T3). OHRQoL was measured through the Early Childhood Oral Health Impact Scale (ECOHIS) and Child Perceptions Questionnaire (CPQ8-10 and CPQ11-14), according to the age group. Dental caries was evaluated using the International Caries Detection and Assessment System (ICDAS) in the three waves. Socioeconomic variables and other factors related to oral health (frequency of toothbrushing and toothache) were also collected. Structural equation modeling was used to estimate the direct and indirect effects among the variables over ten years. RESULTS: A total of 449 and 429 children were reevaluated at T2 and T3 (positive response rates of 70.3% and 67.1%, respectively). Dental caries in T1 and T2 directly predicted the occurrence of a worse OHRQoL in the respective follow-up periods. Dental caries at T3 indirectly predicted a worse OHRQoL (T3), via toothache. Dental caries at T1 and T2 directly predicted the occurrence of dental caries at T3, while a worse OHRQoL at T2 directly predicted a worse OHRQoL at T3. CONCLUSION: Dental caries negatively impacts, directly and indirectly, the OHRQoL from early childhood to adolescence.

Dental caries in children and vitamin D deficiency: a narrative review.

Dental caries represents one of the most prevalent health problems in childhood. Numerous studies have assessed that vitamin D deficiency is highly related to dental caries in primary and permanent teeth in children. The aim of this study is to elaborate a narrative review about proposed mechanisms by which vitamin D deficiency interacts with dental caries process in children. Vitamin D deficiency during pregnancy may cause intrauterine enamel defects, and through childhood is accompanied by insufficient activity of antibacterial peptides, decreased saliva secretion, and a low level of calcium in saliva.  Conclusion: In conclusion, vitamin D deficiency would increase the risk of caries in the primary and/or permanent dentition. Relationship between vitamin D deficiency and dental caries is evident enough for vitamin D deficiency to be considered as a risk factor for dental caries in children. Optimal levels of vitamin D throughout pregnancy and childhood may be considered an additional preventive measure for dental caries in the primary and permanent dentition.

Association between prenatal vitamin D deficiency with dental caries in infants and children: a systematic review and meta-analysis.

Prenatal vitamin D (PVD) is a vital micronutrient for dental caries (DCs). The association between prenatal vitamin D deficiencies (PVDD) and DCs in children has been conflicting in different reports. This meta-analysis aimed to investigate the association between PVDD and DCs in children for the first time. We searched PubMed, Scopus, Web of Sciences, Embase, and Scholar databases to find relevant studies based on mesh terms from 2000 to October 2023. This study was conducted based on the 2020 version of the PRISMA checklist. Cochran's Q and I2 tests were used to evaluate heterogeneity between studies. Egger's test was used to evaluate publication bias. The effect size of the association between PVDD and DCs was reported by the odds ratio (OR) at the 95% confidence interval (95% CI).Twelve studies, including 11,021 participants, were reviewed. The pooled prevalence of PVDD was estimated at 4353 (32%). The prevalence of DCs in children of mothers with and without PVDD was 44% and 25%, respectively. PVDD was significantly associated with an increased risk of DCs in children (OR: 1.35, 95% CI (1.22, 1.47), I2 = 86.6%). The association of DCs with PVDD was different based on gestational age groups, children's age groups, and vitamin D levels. This meta-analysis showed PVDD can be associated with an increased risk of DCs in children, especially in mothers with prenatal vitamin D levels ≤ 35 nmol/L. Adequate vitamin D levels throughout pregnancy can help prevent DCs in children.