In recent years, unprecedented gains in the understanding of the biology and mechanisms underlying human health and disease have been made. In the domain of oral health, although much remains to be ...learned, the complex interactions between different systems in play have begun to unravel: host genome, oral microbiome with its transcriptome, proteome and metabolome, and more distal influences, including relevant behaviors and environmental exposures. A reasonable expectation is that this emerging body of knowledge can help improve the oral health and optimize care for individuals and populations. These goals are articulated by the National Institutes of Health as “precision medicine” and the elimination of health disparities. Key processes in these efforts are the discovery of causal factors or mechanistic pathways and the identification of individuals or population segments that are most likely to develop (any or severe forms of) oral disease. This article critically reviews the fundamental concepts of risk assessment and outcome prediction, as they relate to early childhood caries (ECC)—a common complex disease with significant negative impacts on children, their families, and the health system. The article highlights recent work and advances in methods available to estimate caries risk and derive person-level caries propensities. It further discusses the reasons for their limited utility in predicting individual ECC outcomes and informing clinical decision making. Critical issues identified include the misconception of defining dental caries as a tooth or surface-level condition versus a person-level disease; the fallacy of applying population-level parameters to individuals, termed privatization of risk; and the inadequacy of using frequentist versus Bayesian modeling approaches to derive individual disease propensity estimates. The article concludes with the notion that accurate caries risk assessment at the population level and “precision dentistry” at the person level are both desirable and achievable but must be based on high-quality longitudinal data and rigorous methodology.
In recent years, unprecedented gains in the understanding of the biology and mechanisms underlying human health and disease have been made. In the domain of oral health, although much remains to be ...learned, the complex interactions between different systems in play have begun to unravel: host genome, oral microbiome with its transcriptome, proteome and metabolome, and more distal influences, including relevant behaviors and environmental exposures. A reasonable expectation is that this emerging body of knowledge can help improve the oral health and optimize care for individuals and populations. These goals are articulated by the National Institutes of Health as “precision medicine” and the elimination of health disparities. Key processes in these efforts are the discovery of causal factors or mechanistic pathways and the identification of individuals or population segments that are most likely to develop (any or severe forms of) oral disease. This article critically reviews the fundamental concepts of risk assessment and outcome prediction, as they relate to early childhood caries (ECC)—a common complex disease with significant negative impacts on children, their families, and the health system. The article highlights recent work and advances in methods available to estimate caries risk and derive person-level caries propensities. It further discusses the reasons for their limited utility in predicting individual ECC outcomes and informing clinical decision making. Critical issues identified include the misconception of defining dental caries as a tooth or surface-level condition versus a person-level disease; the fallacy of applying population-level parameters to individuals, termed privatization of risk; and the inadequacy of using frequentist versus Bayesian modeling approaches to derive individual disease propensity estimates. The article concludes with the notion that accurate caries risk assessment at the population level and “precision dentistry” at the person level are both desirable and achievable but must be based on high-quality longitudinal data and rigorous methodology.
Understanding the “code of life” and mapping the human genome have been monumental and era-defining scientific landmarks—analogous to setting foot on the moon. The last century has been characterized ...by exponential advances in our understanding of the biological and specifically molecular basis of health and disease. The early part of the 20th century was marked by fundamental theoretical and scientific advances in understanding heredity, the identification of the DNA molecule and genes, and the elucidation of the central dogma of biology. The second half was characterized by experimental and increasingly molecular investigations, including clinical and population applications. The completion of the Human Genome Project in 2003 and the continuous technological advances have democratized access to this information and the ability to generate health and disease association data; however, the realization of genomic and precision medicine, to practically improve people’s health, has lagged. The oral health domain has made great strides and substantially benefited from the last century of advances in genetics and genomics. Observations regarding a hereditary component of dental caries were reported as early as the 1920s. Subsequent breakthroughs were made in the discovery of genetic causes of rare diseases, such as ectodermal dysplasias, orofacial clefts, and other craniofacial and dental anomalies. More recently, genome-wide investigations have been conducted and reported for several diseases and traits, including periodontal disease, dental caries, tooth agenesis, cancers of the head and neck, orofacial pain, temporomandibular disorders, and craniofacial morphometrics. Gene therapies and gene editing with CRISPR/Cas represent the latest frontier surpassed in the era of genomic medicine. Amid rapid genomics progress, several challenges and opportunities lie ahead. Importantly, systematic efforts supported by implementation science are needed to realize the full potential of genomics, including the improvement of public and practitioner genomics literacy, the promotion of individual and population oral health, and the reduction of disparities.
During the past decades, remarkable progress has been made in the understanding of the molecular basis of the 2 most common oral diseases, dental caries and periodontal disease. Improvements in our ...knowledge of the diseases’ underlying biology have illuminated previously unrecognized aspects of their pathogenesis. Importantly, the key role of the oral (supragingival and subgingival) microbiome is now well recognized, and both diseases are now best understood as dysbiotic. From a host susceptibility standpoint, some progress has been made in dissecting the “hyperinflammatory” trait and other pathways of susceptibility underlying periodontitis, and novel susceptibility loci have been reported for dental caries. Nevertheless, there is a long road to the translation of these findings and the realization of precision oral health. There is promise and hope that the rapidly increasing capacity of generating multiomics data layers and the aggregation of study samples and cohorts comprising thousands of participants will accelerate the discovery and translation processes. A first key element in this process has been the identification and interrogation of biologically informed disease traits—these “deep” or “precise” traits have the potential of revealing biologically homogeneous disease signatures and genetic susceptibility loci that might present with overlapping or heterogeneous clinical signs. A second key element has been the formation of international consortia with the goals of combining and harmonizing oral health data of thousands of individuals from diverse settings—these “wide” collaborative approaches leverage the power of large sample sizes and are aimed toward the discovery or validation of genetic influences that would otherwise be impossible to detect. Importantly, advancements via these directions require an unprecedented engagement of systems biology and team science models. The article highlights novel insights into the molecular basis of dental caries and chronic periodontitis that have been gained from recent and ongoing studies involving “deep” and “wide” analytical approaches.
Health disparities are preventable differences in the burden of disease or opportunities to achieve optimal health that are experienced by socially disadvantaged population groups. Reducing health ...disparities has been identified as an ethical imperative by the World Health Organization’s Commission on Social Determinants of Health and numerous other national and international bodies. Significant progress has been made over the past years in identifying vulnerable groups, and ‘distal’ factors including political, economic, social, and community characteristics are now considered pivotal. It is thus unsurprising that the remarkable advances in the science and practice of dentistry have not led to notable reductions in oral health disparities. In this review, we summarize recent work and emphasize the need for a solid theoretical framing to guide oral health disparities research. We provide a theoretical framework outlining pathways that operate across the continuum of oral health determinants during the lifecourse and highlight potential areas for intervention. Because oral health disparities emanate from the unequal distribution of social, political, economic, and environmental resources, tangible progress is likely to be realized only by a global movement and concerted efforts by all stakeholders, including policymakers, the civil society, and academic, professional, and scientific bodies.
The aim of this study was to systematically appraise the existing literature on the yet-unclear heritability of gingivitis and periodontitis. This review was conducted following the PRISMA ...guidelines. A search was conducted through the electronic databases Medline, Embase, LILACS, Cochrane Library, Open Grey, Google Scholar, and Research Gate, as complemented by a hand search, for human studies reporting measures of heritability of gingivitis and periodontitis. A total of 9,037 papers were initially identified from combined databases and 10,810 on Google Scholar. After full-text reading, 28 articles met the inclusion criteria and were carried forward to data abstraction. The reviewed data included information from >50,000 human subjects. Meta-analyses were performed by grouping studies based on design and outcome. Heritability (H2) of periodontitis was estimated at 0.38 (95% CI, 0.34 to 0.43; I2 = 12.9%) in twin studies, 0.15 (95% CI, 0.06 to 0.24; I2 = 0%) in other family studies, and 0.29 (95% CI, 0.21 to 0.38; I2 = 61.2%) when twin and other family studies were combined. Genome-wide association studies detected a lower heritability estimate of 0.07 (95% CI, −0.02 to 0.15) for combined definitions of periodontitis, increasing with disease severity and when the interaction with smoking was included. Furthermore, heritability tended to be lower among older age groups. Heritability for the self-reported gingivitis trait was estimated at 0.29 (95% CI, 0.22 to 0.36; I2 = 37.6%), while it was not statistically significant for clinically measured gingivitis. This systematic review brings forward summary evidence to confirm that up to a third of the periodontitis variance in the population is due to genetic factors. This seems consistent across the different studied populations and increases with disease severity. In summary, up to a third of the variance of periodontitis in the population is due to genetic factors, with higher heritability for more severe disease.
Periodontitis is one of the most prevalent chronic inflammatory diseases and is induced by the interaction between oral microorganisms and the host immune system. Plasma cells are of special interest ...in chronic periodontitis (CP), as they represent ~50% of infiltrated immune cells in periodontal lesions. Plasma cells constitute the only known cell type capable of antibody production; however, recent evidence supports an emerging role for distinct sets of plasma cells in cytokine production. However, the presence of cytokine-producing plasma cells in CP is unknown. In this study, we used immunohistochemistry to detect significantly elevated levels of IL-35 and IL-37 (2 recently identified anti-inflammatory cytokines) in CP gingival tissue as compared with healthy tissue. Remarkably, we demonstrate that CD138+ CD38+ plasma cells are the major immune cell type in CP gingival tissues and that these cells produce IL-35 and IL-37. We used immunofluorescence and confocal microscopy analysis to identify a subset of plasma cells with robust cytoplasmic expression of IL-37—we denote this subset as IL-37-producing plasma cells (CD138+CD38+PIL-37). Another subset of plasma cells coproduces IL-35 and IL-37 and is denoted as IL-37/IL-35-coproducing plasma cells (CD138+CD38+PIL-35/IL-37). We determined that these 2 plasma cell subsets are IgG+plasma cells. Moreover, we show that human recombinant IL-35 and IL-37 exhibit a dose-dependent inhibition of osteoclast formation in vitro (~78.9% and 97.7% inhibition in 300 ng/mL of IL-35 and IL-37, respectively, P < 0.05). Overall, our findings suggest that PIL-37 and PIL-35/IL-37 exist as subsets of plasma cells in CP lesions and that these 2 new types of plasma cells may regulate periodontitis pathogenesis by inhibiting alveolar bone loss through directly blocking osteoclast formation. Importantly, these data suggest a novel role of plasma cells and offer potential new mechanistic and regulatory targets to be investigated in the context of periodontal health and disease.
Poor oral hygiene has been proposed to contribute to head and neck cancer (HNC) risk, although causality and independency of some indicators are uncertain. This study investigates the relationship of ...five oral hygiene indicators with incident HNCs.
In a pooled analysis of 8925 HNC cases and 12 527 controls from 13 studies participating in the International Head and Neck Cancer Epidemiology Consortium, comparable data on good oral hygiene indicators were harmonized. These included: no denture wear, no gum disease (or bleeding), <5 missing teeth, tooth brushing at least daily, and visiting a dentist ≥once a year. Logistic regression was used to estimate the effects of each oral hygiene indicator and cumulative score on HNC risk, adjusting for tobacco smoking and alcohol consumption.
Inverse associations with any HNC, in the hypothesized direction, were observed for <5 missing teeth odds ratio (OR) = 0.78; 95% confidence interval (CI) 0.74, 0.82, annual dentist visit (OR = 0.82; 95% CI 0.78, 0.87), daily tooth brushing (OR = 0.83, 95% CI 0.79, 0.88), and no gum disease (OR = 0.94; 95% CI 0.89, 0.99), and no association was observed for wearing dentures. These associations were relatively consistent across specific cancer sites, especially for tooth brushing and dentist visits. The population attributable fraction for ≤ 2 out of 5 good oral hygiene indicators was 8.9% (95% CI 3.3%, 14%) for oral cavity cancer.
Good oral hygiene, as characterized by few missing teeth, annual dentist visits, and daily tooth brushing, may modestly reduce the risk of HNC.
Pathological shifts of the human microbiome are characteristic of many diseases, including chronic periodontitis. To date, there is limited evidence on host genetic risk loci associated with ...periodontal pathogen colonization. We conducted a genome-wide association (GWA) study among 1,020 white participants of the Atherosclerosis Risk in Communities Study, whose periodontal diagnosis ranged from healthy to severe chronic periodontitis, and for whom “checkerboard” DNA-DNA hybridization quantification of 8 periodontal pathogens was performed. We examined 3 traits: “high red” and “high orange” bacterial complexes, and “high” Aggregatibacter actinomycetemcomitans (Aa) colonization. Genotyping was performed on the Affymetrix 6.0 platform. Imputation to 2.5 million markers was based on HapMap II-CEU, and a multiple-test correction was applied (genome-wide threshold of p < 5 × 10−8). We detected no genome-wide significant signals. However, 13 loci, including KCNK1, FBXO38, UHRF2, IL33, RUNX2, TRPS1, CAMTA1, and VAMP3, provided suggestive evidence (p < 5 × 10−6) of association. All associations reported for “red” and “orange” complex microbiota, but not for Aa, had the same effect direction in a second sample of 123 African-American participants. None of these polymorphisms was associated with periodontitis diagnosis. Investigations replicating these findings may lead to an improved understanding of the complex nature of host-microbiome interactions that characterizes states of health and disease.
The aim of this study was to investigate the association of female caregivers’ oral health literacy with their knowledge, behaviors, and the reported oral health status of their young children. Data ...on caregivers’ literacy, knowledge, behaviors, and children’s oral health status were used from structured interviews with 1158 caregiver/child dyads from a low-income population. Literacy was measured with REALD-30. Caregivers’ and children’s median ages were 25 yrs (range = 17-65) and 15 mos (range = 1-59), respectively. The mean literacy score was 15.8 (SD = 5.3; range = 1-30). Adjusted for age, education, and number of children, low literacy scores (< 13 REALD-30) were associated with decreased knowledge (OR = 1.86; 95% CI = 1.41, 2.45) and poorer reported oral health status (OR = 1.44; 95% CI = 1.02, 2.05). Lower caregiver literacy was associated with deleterious oral health behaviors, including nighttime bottle use and no daily brushing/cleaning. Caregiver oral health literacy has a multidimensional impact on reported oral health outcomes in infants and young children.
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