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Defining the oral microbiome by whole-genome sequencing and resistome analysis: the complexity of the healthy picture. Caselli Elisabetta,Fabbri Chiara,D'Accolti Maria,Soffritti Irene,Bassi Cristian,Mazzacane Sante,Franchi Maurizio BMC microbiology BACKGROUND:The microbiome of the oral cavity is the second-largest and diverse microbiota after the gut, harboring over 700 species of bacteria and including also fungi, viruses, and protozoa. With its diverse niches, the oral cavity is a very complex environment, where different microbes preferentially colonize different habitats. Recent data indicate that the oral microbiome has essential functions in maintaining oral and systemic health, and the emergence of 16S rRNA gene next-generation sequencing (NGS) has greatly contributed to revealing the complexity of its bacterial component. However, a detailed site-specific map of oral microorganisms (including also eukaryotes and viruses) and their relative abundance is still missing. Here, we aimed to obtain a comprehensive view of the healthy oral microbiome (HOM), including its drug-resistance features. RESULTS:The oral microbiome of twenty healthy subjects was analyzed by whole-genome sequencing (WGS) and real-time quantitative PCR microarray. Sampled oral micro-habitat included tongue dorsum, hard palate, buccal mucosa, keratinized gingiva, supragingival and subgingival plaque, and saliva with or without rinsing. Each sampled oral niche evidenced a different microbial community, including bacteria, fungi, and viruses. Alpha-diversity evidenced significant differences among the different sampled sites (p < 0.0001) but not among the enrolled subjects (p = 0.876), strengthening the notion of a recognizable HOM. Of note, oral rinse microbiome was more representative of the whole site-specific microbiomes, compared with that of saliva. Interestingly, HOM resistome included highly prevalent genes conferring resistance to macrolide, lincosamides, streptogramin, and tetracycline. CONCLUSIONS:The data obtained in 20 subjects by WGS and microarray analysis provide for the first time a comprehensive view of HOM and its resistome, contributing to a deeper understanding of the composition of oral microbiome in the healthy subject, and providing an important reference for future studies, allowing to identify microbial signatures related to functional and metabolic alterations associated with diseases, potentially useful for targeted therapies and precision medicine. 10.1186/s12866-020-01801-y
Dynamic navigation may be used for most implant surgery scenarios due to its satisfactory accuracy. The journal of evidence-based dental practice ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION:Wei SM, Zhu Y, Wei JX, Zhang CN, Shi JY, Lai HC. Accuracy of dynamic navigation in implant surgery: A systematic review and meta-analysis. Clin Oral Implants Res. 2021 Apr;32(4):383-393. doi: 10.1111/clr.13719. SOURCE OF FUNDING:Shanghai Jiao Tong University School of Medicine (grant no. DLY201822); Shanghai Clinical Research Center for Oral Diseases (grant no. 19,411,950,100); Clinical Research Plan of SHDC (grant no. 16CR3033A). TYPE OF STUDY/DESIGN:Systematic review with meta-analysis. 10.1016/j.jebdp.2022.101797
Dysbiosis and Ecotypes of the Salivary Microbiome Associated With Inflammatory Bowel Diseases and the Assistance in Diagnosis of Diseases Using Oral Bacterial Profiles. Xun Zhe,Zhang Qian,Xu Tao,Chen Ning,Chen Feng Frontiers in microbiology Inflammatory bowel diseases (IBDs) are chronic, idiopathic, relapsing disorders of unclear etiology affecting millions of people worldwide. Aberrant interactions between the human microbiota and immune system in genetically susceptible populations underlie IBD pathogenesis. Despite extensive studies examining the involvement of the gut microbiota in IBD using culture-independent techniques, information is lacking regarding other human microbiome components relevant to IBD. Since accumulated knowledge has underscored the role of the oral microbiota in various systemic diseases, we hypothesized that dissonant oral microbial structure, composition, and function, and different community ecotypes are associated with IBD; and we explored potentially available oral indicators for predicting diseases. We examined the 16S rRNA V3-V4 region of salivary bacterial DNA from 54 ulcerative colitis (UC), 13 Crohn's disease (CD), and 25 healthy individuals using Illumina sequencing. Distinctive sample clusters were driven by disease or health based on principal coordinate analysis (PCoA) of both the Operational Taxonomic Unit profile and Kyoto Encyclopedia of Genes and Genomes pathways. Comparisons of taxa abundances revealed enrichment of () and in UC and () in CD, accompanied by depletion of and in UC and () and in CD, most of which have been demonstrated to exhibit the same variation tendencies in the gut of IBD patients. IBD-related oral microorganisms were associated with white blood cells, reduced basic metabolic processes, and increased biosynthesis and transport of substances facilitating oxidative stress and virulence. Furthermore, UC and CD communities showed robust sub-ecotypes that were not demographic or severity-specific, suggesting their value for future applications in precision medicine. Additionally, indicator species analysis revealed several genera indicative of UC and CD, which were confirmed in a longitudinal cohort. Collectively, this study demonstrates evident salivary dysbiosis and different ecotypes in IBD communities and provides an option for identifying at-risk populations, not only enhancing our understanding of the IBD microbiome apart from the gut but also offering a clinically useful strategy to track IBD as saliva can be sampled conveniently and non-invasively. 10.3389/fmicb.2018.01136
The future of research in craniofacial biology and what this will mean for oral health professional education and clinical practice. Slavkin H C Australian dental journal Today, and looking to the future, scientific discoveries from cellular, developmental and molecular biology inform our understanding of cell, tissue and organ morphogenesis as exemplified in skin, bone, cartilage, dentine, enamel, muscle, nerve and many organs such as salivary glands and teeth. Present day biomedical science yields principles for the biomimetic design and fabrication of cells, tissues and organs. Bioengineering has become a strategy that can 'mimic' biological processes, and inform clinical procedures for tissue and organ replacements. The future of regenerative craniofacial biology holds enormous promise for the diagnosis and treatment of congenital birth defects, traumatic injuries, degenerative chronic diseases as well as for Mendelian single gene and complex multigene diseases and disorders. The past 50 years have heralded the completion of the human genome and the introduction of 'personalized medicine and dentistry', the utilization of stem cell therapy for an array of diseases and disorders, the 'proof of principle' to reverse select inherited diseases such as anhidrotic ectodermal dysplasia (ED), and the fruits from interdisciplinary research drawn from the diverse biomedical sciences. Looking to the future, we can readily anticipate as major goals to emphasize the clinician's role in identifying clinical phenotypes that can lead to differential diagnosis, and rejuvenate missing or damaged tissues by establishing processes for the utilization of gene, cell and/or protein therapies. The future is replete with remarkable opportunities to enhance clinical outcomes for congenital as well as acquired craniofacial malformations. Clinicians play a pivotal role because critical thinking and sound clinical acumen substantially improve diagnostic precision and thereby clinical health outcomes. 10.1111/adj.12105
An aMMP-8 Point-of-Care and Questionnaire Based Real-Time Diagnostic Toolkit for Medical Practitioners. Räisänen Ismo T,Lähteenmäki Hanna,Gupta Shipra,Grigoriadis Andreas,Sahni Vaibhav,Suojanen Juho,Seppänen Hanna,Tervahartiala Taina,Sakellari Dimitra,Sorsa Timo Diagnostics (Basel, Switzerland) The aim of this cross-sectional study is to propose an efficient strategy based on biomarkers adjunct with an interview/questionnaire covering risk factors for periodontitis for the identification of undiagnosed periodontitis by medical professionals. Active matrix metalloproteinase (aMMP)-8 levels in mouthrinse were analyzed by a point-of-care (PoC)/chairside lateral-flow immunotest, and salivary total MMP-8, total MMP-9 and calprotectin levels were analyzed by enzyme-linked immunosorbent assays (ELISAs) and active MMP-9 by gelatin zymography for 149 Greek patients. Patients underwent a full-mouth oral health examination for diagnosis according to the 2018 classification system of periodontal diseases. In addition, patient characteristics (risk factors: age, gender, education level, smoking and body mass index) were recorded. Receiver operating curve (ROC) analysis indicated better diagnostic precision to identify undiagnosed periodontitis for oral fluid biomarkers in adjunct with an interview/questionnaire compared with a plain questionnaire (i.e., risk factors): aMMP-8 AUC (95% confidence interval) = 0.834 (0.761-0.906), total MMP-8 = 0.800 (0.722-0.878), active MMP-9 = 0.787 (0.704-0.870), total MMP-9 = 0.773 (0.687-0.858) and calprotectin = 0.773 (0.687-0.858) vs. questionnaire = 0.764 (0.676-0.851). The findings of this study suggest that oral fluid biomarker analysis, such as a rapid aMMP-8 PoC immunotest, could be used as an adjunct to an interview/questionnaire to improve the precision of timely identification of asymptomatic, undiagnosed periodontitis patients by medical professionals. This strategy appears to be viable for referring patients to a dentist for diagnosis and treatment need assessment. 10.3390/diagnostics11040711
Progress in oral personalized medicine: contribution of 'omics'. Glurich Ingrid,Acharya Amit,Brilliant Murray H,Shukla Sanjay K Journal of oral microbiology BACKGROUND:Precision medicine (PM), representing clinically applicable personalized medicine, proactively integrates and interprets multidimensional personal health data, including clinical, 'omics', and environmental profiles, into clinical practice. Realization of PM remains in progress. OBJECTIVE:The focus of this review is to provide a descriptive narrative overview of: 1) the current status of oral personalized medicine; and 2) recent advances in genomics and related 'omic' and emerging research domains contributing to advancing oral-systemic PM, with special emphasis on current understanding of oral microbiomes. DESIGN:A scan of peer-reviewed literature describing oral PM or 'omic'-based research conducted on humans/data published in English within the last 5 years in journals indexed in the PubMed database was conducted using mesh search terms. An evidence-based approach was used to report on recent advances with potential to advance PM in the context of historical critical and systematic reviews to delineate current state-of-the-art technologies. Special focus was placed on oral microbiome research associated with health and disease states, emerging research domains, and technological advances, which are positioning realization of PM. RESULTS:This review summarizes: 1) evolving conceptualization of personalized medicine; 2) emerging insight into roles of oral infectious and inflammatory processes as contributors to both oral and systemic diseases; 3) community shifts in microbiota that may contribute to disease; 4) evidence pointing to new uncharacterized potential oral pathogens; 5) advances in technological approaches to 'omics' research that will accelerate PM; 6) emerging research domains that expand insights into host-microbe interaction including inter-kingdom communication, systems and network analysis, and salivaomics; and 7) advances in informatics and big data analysis capabilities to facilitate interpretation of host and microbiome-associated datasets. Furthermore, progress in clinically applicable screening assays and biomarker definition to inform clinical care are briefly explored. CONCLUSION:Advancement of oral PM currently remains in research and discovery phases. Although substantive progress has been made in advancing the understanding of the role of microbiome dynamics in health and disease and is being leveraged to advance early efforts at clinical translation, further research is required to discern interpretable constituency patterns in the complex interactions of these microbial communities in health and disease. Advances in biotechnology and bioinformatics facilitating novel approaches to rapid analysis and interpretation of large datasets are providing new insights into oral health and disease, potentiating clinical application and advancing realization of PM within the next decade. 10.3402/jom.v7.28223
Interpretable machine learning framework reveals microbiome features of oral disease. Microbiological research BACKGROUND:Although the oral microbiome plays an important role in the progression of oral diseases, the microbes closely related to these diseases remain largely uncharacterized. RESULTS:We collected saliva samples from 140 individuals and performed 16 S amplicon sequencing. An interpretable machine learning framework for imbalanced high-dimensional big data of clinical microbial samples was developed to identify 14 oral microbiome features associated with oral diseases. Microbiome risk scores (MRSs) with the identified features were constructed with SHapley Additive exPlanations (SHAP). Correlations of the MRSs with individual physiological indicators and lifestyle habits were calculated. CONCLUSION:Our results reveal a set of oral microbiome features associated with oral diseases. Our study demonstrates the feasibility of preventing oral disease through lifestyle interventions and provides a reference method for the era of precision medicine aimed at individualized medicine. 10.1016/j.micres.2022.127198
Interconnections Between the Oral and Gut Microbiomes: Reversal of Microbial Dysbiosis and the Balance Between Systemic Health and Disease. Microorganisms The human microbiota represents a complex array of microbial species that influence the balance between the health and pathology of their surrounding environment. These microorganisms impart important biological benefits to their host, such as immune regulation and resistance to pathogen colonization. Dysbiosis of microbial communities in the gut and mouth precede many oral and systemic diseases such as cancer, autoimmune-related conditions, and inflammatory states, and can involve the breakdown of innate barriers, immune dysregulation, pro-inflammatory signaling, and molecular mimicry. Emerging evidence suggests that periodontitis-associated pathogens can translocate to distant sites to elicit severe local and systemic pathologies, which necessitates research into future therapies. Fecal microbiota transplantation, probiotics, prebiotics, and synbiotics represent current modes of treatment to reverse microbial dysbiosis through the introduction of health-related bacterial species and substrates. Furthermore, the emerging field of precision medicine has been shown to be an effective method in modulating host immune response through targeting molecular biomarkers and inflammatory mediators. Although connections between the human microbiome, immune system, and systemic disease are becoming more apparent, the complex interplay and future innovations in treatment modalities will become elucidated through continued research and cross-disciplinary collaboration. 10.3390/microorganisms9030496
Nucleoside analogs: ready to enter the era of precision medicine? Ciccolini Joseph,Serdjebi Cindy,Le Thi Thu Hau,Lacarelle Bruno,Milano Gerard,Fanciullino Raphaelle Expert opinion on drug metabolism & toxicology INTRODUCTION:The term 'precision medicine' has garnered significant attention in the oncological setting in relation to attempts to optimize anticancer treatment. Precision medicine is mostly associated with oral targeted therapies and biotherapies, however, to date classic cytotoxics still remain the backbone of most regimens for treating solid tumors or in hematology, both in children and in adults. Among the existing cytotoxic therapies, nucleosides are widely used for treating a variety of cancerous diseases, alone or as part of combination therapies. AREAS COVERED:Several markers at the tumor or the germinal levels have been identified as being associated with clinical outcome (e.g. CDA, DPD, EONFS1, hENT1, TYMS, MTHFR), however little effort has been made to implement bioguided therapy with nucleoside analogs. Still, growing clinical evidence has demonstrated how the efficacy-toxicity balance of these drugs could be improved by developing bioguided strategies at the bedside. This review covers the current knowledge regarding putative markers to be used with nucleoside analogs, what is known on their pharmacokinetic/pharmacodynamic relationships, and provides clues for implementing precision medicine with those old, yet pivotal drugs. EXPERT OPINION:Through a variety of strategies ranging from pharmacogenetics, tumor genomics and pharmacokinetically-driven adaptive dosing procedures, nucleoside analogs could enter the era of precision medicine in oncology. 10.1080/17425255.2016.1192128
Dental Mesenchymal Stem Cell-Based Translational Regenerative Dentistry: From Artificial to Biological Replacement. Marei Mona K,El Backly Rania M Frontiers in bioengineering and biotechnology Dentistry is a continuously changing field that has witnessed much advancement in the past century. Prosthodontics is that branch of dentistry that deals with replacing missing teeth using either fixed or removable appliances in an attempt to simulate natural tooth function. Although such "replacement therapies" appear to be easy and economic they fall short of ever coming close to their natural counterparts. Complications that arise often lead to failures and frequent repairs of such devices which seldom allow true physiological function of dental and oral-maxillofacial tissues. Such factors can critically affect the quality of life of an individual. The market for dental implants is continuously growing with huge economic revenues. Unfortunately, such treatments are again associated with frequent problems such as peri-implantitis resulting in an eventual loss or replacement of implants. This is particularly influential for patients having co-morbid diseases such as diabetes or osteoporosis and in association with smoking and other conditions that undoubtedly affect the final treatment outcome. The advent of tissue engineering and regenerative medicine therapies along with the enormous strides taken in their associated interdisciplinary fields such as stem cell therapy, biomaterial development, and others may open arenas to enhancing tissue regeneration via designing and construction of patient-specific biological and/or biomimetic substitutes. This review will overview current strategies in regenerative dentistry while overviewing key roles of dental mesenchymal stem cells particularly those of the dental pulp, until paving the way to precision/translational regenerative medicine therapies for future clinical use. 10.3389/fbioe.2018.00049
Differential genotypes of TNF-α and IL-10 for immunological diagnosis in discoid lupus erythematosus and oral lichen planus: A narrative review. Frontiers in immunology Discoid lupus erythematosus and oral lichen planus are chronic systemic immune system-mediated diseases with unclear etiology and pathogenesis. The oral mucosa is the common primary site of pathogenesis in both, whereby innate and adaptive immunity and inflammation play crucial roles. The clinical manifestations of discoid lupus erythematosus on the oral mucosa are very similar to those of oral lichen planus; therefore, its oral lesion is classified under oral lichenoid lesions. In practice, the differential diagnosis of discoid lupus erythematosus and oral lichen planus has always relied on the clinical manifestations, with histopathological examination as an auxiliary diagnostic tool. However, the close resemblance of the clinical manifestations and histopathology proves challenging for accurate differential diagnosis and further treatment. In most cases, dentists and pathologists fail to distinguish between the conditions during the early stages of the lesions. It should be noted that both are considered to be precancerous conditions, highlighting the significance of early diagnosis and treatment. In the context of unknown etiology and pathogenesis, we suggest a serological and genetic diagnostic method based on TNF-α and IL-10. These are the two most common cytokines produced by the innate and adaptive immune systems and they play a fundamental role in maintaining immune homeostasis and modulating inflammation. The prominent variability in their expression levels and gene polymorphism typing in different lesions compensates for the low specificity of current conventional diagnostic protocols. This new diagnostic scheme, starting from the immunity and inflammation of the oral mucosa, enables simultaneous comparison of discoid lupus erythematosus and oral lichen planus. With relevant supportive evidence, this information can enhance physicians' understanding of the two diseases, contribute to precision medicine, and aid in prevention of precancerous conditions. 10.3389/fimmu.2022.967281
The Oral Host-Microbial Interactome: An Ecological Chronometer of Health? Trends in microbiology An increasing number of studies reveal that host-microbial interactome networks are coordinated, impacting human health and disease. Recently, several lines of evidence have revealed associations between the acquisition of a complex microbiota and adaptive immunity, supporting that host-microbiota symbiotic relationships have evolved as a means to maintain homeostasis where the role of the microbiota is to promote and educate the immune system. Here, we hypothesize an oral host-microbial interactome that could serve as an ecological chronometer of health and disease, with specific focus on caries, periodontal diseases, and cancer. We also review the current state of the art on the human oral microbiome and its correlations with host innate immunity, and host cytokine control, with the goal of using this information for disease prediction and designing novel treatments for local and systemic dysbiosis. In addition, we discuss new insights into the role of novel host-microbial signals as potential biomarkers, and their relevance for the future of precision dentistry and medicine. 10.1016/j.tim.2020.11.004
Clinical Perspectives of Non-Coding RNA in Oral Inflammatory Diseases and Neuropathic Pain: A Narrative Review. International journal of molecular sciences Non-coding RNAs (ncRNAs) represent a research hotspot by playing a key role in epigenetic and transcriptional regulation of diverse biological functions and due to their involvement in different diseases, including oral inflammatory diseases. Based on ncRNAs' suitability for salivary biomarkers and their involvement in neuropathic pain and tissue regeneration signaling pathways, the present narrative review aims to highlight the potential clinical applications of ncRNAs in oral inflammatory diseases, with an emphasis on salivary diagnostics, regenerative dentistry, and precision medicine for neuropathic orofacial pain. 10.3390/ijms23158278
From high definition precision healthcare to precision public oral health: opportunities and challenges. Slavkin Harold C Journal of public health dentistry In anticipation of a major transformation in healthcare, this review provides highlights that anticipate the near future for oral public health (and beyond). Personalized or precision healthcare reflects the expectation that advances in genomics, imaging, and other domains will extend our risk assessment, diagnostic, and prognostic capabilities, and enables more effective prevention and therapeutic options for all Americans. Meanwhile, the current healthcare system does not meet cost, access, or quality criteria for all Americans. It is now an imperative that the success of "smart," quality, and cost-effective high definition precision healthcare requires a public health perspective for several reasons: a) to enhance generalizability, b) to assess methods of implementation, and c) to focus on both risk and prevention in large and small populations, thereby providing a balance between the generation of long-term knowledge and short-term health gains. Sensitivity and resolution, reasonable cost, access to all Americans, coordinated comprehensive care, and advances in whole genome sequencing (WGS) and big data analyses, coupled to other advances in biotechnology and digital/artificial intelligence/machine learning devices, and the behavioral, social, and environmental sciences, offer remarkable opportunities to improve the health and wellness of the American people [genotype + phenotype + environment + behavior = high definition healthcare]. The opportunity is to significantly improve the well-being and life expectancy of all people across the lifespan including the least-advantaged people in our society and potentially increase access, reduce the national costs, and improve health outcomes. 10.1111/jphd.12296
Progress in Oral Microbiome Related to Oral and Systemic Diseases: An Update. Lee Yeon-Hee,Chung Sang Wan,Auh Q-Schick,Hong Seung-Jae,Lee Yeon-Ah,Jung Junho,Lee Gi-Ja,Park Hae Jeong,Shin Seung-Il,Hong Ji-Youn Diagnostics (Basel, Switzerland) The human oral microbiome refers to an ecological community of symbiotic and pathogenic microorganisms found in the oral cavity. The oral cavity is an environment that provides various biological niches, such as the teeth, tongue, and oral mucosa. The oral cavity is the gateway between the external environment and the human body, maintaining oral homeostasis, protecting the mouth, and preventing disease. On the flip side, the oral microbiome also plays an important role in the triggering, development, and progression of oral and systemic diseases. In recent years, disease diagnosis through the analysis of the human oral microbiome has been realized with the recent development of innovative detection technology and is overwhelmingly promising compared to the previous era. It has been found that patients with oral and systemic diseases have variations in their oral microbiome compared to normal subjects. This narrative review provides insight into the pathophysiological role that the oral microbiome plays in influencing oral and systemic diseases and furthers the knowledge related to the oral microbiome produced over the past 30 years. A wide range of updates were provided with the latest knowledge of the oral microbiome to help researchers and clinicians in both academic and clinical aspects. The microbial community information can be utilized in non-invasive diagnosis and can help to develop a new paradigm in precision medicine, which will benefit human health in the era of post-metagenomics. 10.3390/diagnostics11071283
Precision periodontal care: from omics discoveries to chairside diagnostics. Clinical oral investigations The interface of molecular science and technology is guiding the transformation of personalized to precision healthcare. The application of proteomics, genomics, transcriptomics, and metabolomics is shaping the suitability of biomarkers for disease. Prior validation of such biomarkers in large and diverse patient cohorts helps verify their clinical usability. Incorporation of molecular discoveries into routine clinical practice relies on the development of customized assays and devices that enable the rapid delivery of analytical data to the clinician, while the patient is still in session. The present perspective review addresses this topic under the prism of precision periodontal care. Selected promising research attempts to innovate technological platforms for oral diagnostics are brought forward. Focus is placed on (a) the suitability of saliva as a conveniently sampled biological specimen for assessing periodontal health, (b) proteomics as a high-throughput approach for periodontal disease biomarker identification, and (c) chairside molecular diagnostic assays as a technological funnel for transitioning from the laboratory benchtop to the clinical point-of-care. 10.1007/s00784-023-04878-7
Genomics of periodontal disease and tooth morbidity. Periodontology 2000 In this review we critically summarize the evidence base and the progress to date regarding the genomic basis of periodontal disease and tooth morbidity (ie, dental caries and tooth loss), and discuss future applications and research directions in the context of precision oral health and care. Evidence for these oral/dental traits from genome-wide association studies first emerged less than a decade ago. Basic and translational research activities in this domain are now under way by multiple groups around the world. Key departure points in the oral health genomics discourse are: (a) some heritable variation exists for periodontal and dental diseases; (b) the environmental component (eg, social determinants of health and behavioral risk factors) has a major influence on the population distribution but probably interacts with factors of innate susceptibility at the person-level; (c) sizeable, multi-ethnic, well-characterized samples or cohorts with high-quality measures on oral health outcomes and genomics information are required to make decisive discoveries; (d) challenges remain in the measurement of oral health and disease, with current periodontitis and dental caries traits capturing only a part of the health-disease continuum, and are little or not informed by the underlying biology; (e) the substantial individual heterogeneity that exists in the clinical presentation and lifetime trajectory of oral disease can be identified and leveraged in a precision medicine framework or, if unappreciated, can hamper translational efforts. In this review we discuss how composite or biologically informed traits may offer improvements over clinically defined ones for the genomic interrogation of oral diseases. We demonstrate the utility of the results of genome-wide association studies for the development and testing of a genetic risk score for severe periodontitis. We conclude that exciting opportunities lie ahead for improvements in the oral health of individual patients and populations via advances in our understanding of the genomic basis of oral health and disease. The pace of new discoveries and their equitable translation to practice will largely depend on investments in the education and training of the oral health care workforce, basic and population research, and sustained collaborative efforts.. 10.1111/prd.12320
The Era of the Genome and Dental Medicine. Journal of dental research 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. 10.1177/0022034519845674
Realizing the clinical utility of saliva for monitoring oral diseases. Periodontology 2000 In the era of personalized/precision health care, additional effort is being expended to understand the biology and molecular mechanisms of disease processes. How these mechanisms are affected by individual genetics, environmental exposures, and behavioral choices will encompass an expanding role in the future of optimally preventing and treating diseases. Considering saliva as an important biological fluid for analysis to inform oral disease detection/description continues to expand. This review provides an overview of saliva as a diagnostic fluid and the features of various biomarkers that have been reported. We emphasize the use of salivary biomarkers in periodontitis and transport the reader through extant literature, gaps in knowledge, and a structured approach toward validating and determine the utility of biomarkers in periodontitis. A summation of the findings support the likelihood that a panel of biomarkers including both host molecules and specific microorganisms will be required to most effectively identify risk for early transition to disease, ongoing disease activity, progression, and likelihood of response to standard periodontal therapy. The goals would be to develop predictive algorithms that serve as adjunctive diagnostic tools which provide the clinician and patient important information for making informed clinical decisions. 10.1111/prd.12581
Social Epigenomics: Conceptualizations and Considerations for Oral Health. Journal of dental research Advances in high-throughput technologies and the generation of multiomics, such as genomic, epigenomic, transcriptomic, and metabolomic data, are paving the way for the biological risk stratification and prediction of oral diseases. When integrated with electronic health records, survey, census, and/or epidemiologic data, multiomics are anticipated to facilitate data-driven precision oral health, or the delivery of the right oral health intervention to the right individuals/populations at the right time. Meanwhile, multiomics may be modified by a multitude of social exposures, cumulatively along the life course and at various time points from conception onward, also referred to as the . For example, adverse exposures, such as precarious social and living conditions and related psychosocial stress among others, have been linked to specific genes being switched "on and off" through epigenetic mechanisms. These in turn are associated with various health conditions in different age groups and populations. This article argues that considering the impact of the socio-exposome in the biological profiling for precision oral health applications is necessary to ensure that definitions of biological risk do not override social ones. To facilitate the uptake of the socio-exposome in multiomics oral health studies and subsequent interventions, 3 pertinent facets are discussed. First, a summary of the epigenetic landscape of oral health is presented. Next, findings from the nondental literature are drawn on to elaborate the pathways and mechanisms that link the socio-exposome with gene expression-or the biological embedding of social experiences through epigenetics. Then, methodological considerations for implementing social epigenomics into oral health research are highlighted, with emphasis on the implications for study design and interpretation. The article concludes by shedding light on some of the current and prospective opportunities for social epigenomics research applied to the study of life course oral epidemiology. 10.1177/00220345221110196
Advances in precision oral health. Beck James D,Philips Kamaira,Moss Kevin,Divaris Kimon,Morelli Thiago,Offenbacher Steven Periodontology 2000 The concept of precision dentistry as it relates to precision medicine is relatively new to the field of oral health. Precision dentistry is a contemporary, multifaceted, data-driven approach to oral health care that uses individual characteristics to stratify similar patients into phenotypic groups. The objective is to provide clinicians with the information that will allow them to improve treatment planning and a patient's response to treatment. Providers that use a precision oral health approach would move away from using an "average treatment" for all patients with a particular diagnosis and move toward more specific treatments for patients within each diagnostic subgroup. Precision dentistry requires a method or a model that places each individual in a subgroup where each member is the same as every other member in relation to the disease of interest. Precision dentistry is a paradigm shift that requires a new way of thinking about diagnostic categories. This approach uses patients' risk factor data (including, but not limited to, genetic, environmental, and health behavioral), rather than expert opinion or clinical presentation alone, to redefine traditional categories of health and disease. We review aspects of current efforts to allow precision dentistry to be realized and focus on one of the major innovations that may help precision dentistry to be practiced by periodontists, the World Workshop Model. Another approach is the Periodontal Profile Class system. These two approaches represent examples of supervised and unsupervised learning systems, respectively. This review compares and contrasts these two learning systems for their ability to classify patients into homogeneous disease and risk groups, as well as their feasibility at achieving the objective of enabling precision dentistry. We conclude that: (a) the World Workshop Model concept of stages and grades works as expected, in that periodontal status appears to be more serious in each successive stage. In addition, the seriousness and the complexity of the disease are greater as the grade increases within each stage. Stages and grades are important for precision dentistry because they consider the risk of future disease and the prognosis, and enable practitioners to use more signs, symptoms, and other associated factors when placing a patient in a diagnostic category; (b) the assignment of stages and grades using unsupervised learning systems is superior to using supervised learning systems for the prediction of 10-year tooth loss and 3-year attachment loss progression. In addition, the unsupervised learning approach (Periodontal Profile Class stages) results in stronger associations between the periodontal phenotypes and systemic diseases and conditions (prevalent diabetes, C-reactive protein, and incident stroke). This probably occurs because an unsupervised learning model produces more data-driven, mutually exclusive, homogeneous groups than a supervised learning model. 10.1111/prd.12314
Microbiome-targeted interventions for the control of oral-gut dysbiosis and chronic systemic inflammation. Trends in molecular medicine Recent research has confirmed the strong connection between imbalances in the oral and gut microbiome (oral-gut dysbiosis), periodontitis, and inflammatory conditions such as diabetes, Alzheimer's disease, and cardiovascular diseases. Microbiome modulation is crucial for preventing and treating several autoimmune and inflammatory diseases, including periodontitis. However, the causal relationships between the microbiome and its derived metabolites that mediate periodontitis and chronic inflammation constitute a notable knowledge gap. Here we review the mechanisms involved in the microbiome-host crosstalk, and describe novel precision medicine for the control of systemic inflammation. As microbiome-targeted therapies begin to enter clinical trials, the success of these approaches relies upon understanding these reciprocal microbiome-host interactions, and it may provide new therapeutic avenues to reduce the risk of periodontitis-associated diseases. 10.1016/j.molmed.2023.08.006
Biosensor and Lab-on-a-chip Biomarker-identifying Technologies for Oral and Periodontal Diseases. Frontiers in pharmacology Periodontitis is a complex multifactorial disease that can lead to destruction of tooth supporting tissues and subsequent tooth loss. The most recent global burden of disease studies highlight that severe periodontitis is one of the most prevalent chronic inflammatory conditions affecting humans. Periodontitis risk is attributed to genetics, host-microbiome and environmental factors. Empirical diagnostic and prognostic systems have yet to be validated in the field of periodontics. Early diagnosis and intervention prevents periodontitis progression in most patients. Increased susceptibility and suboptimal control of modifiable risk factors can result in poor response to therapy, and relapse. The chronic immune-inflammatory response to microbial biofilms at the tooth or dental implant surface is associated with systemic conditions such as cardiovascular disease, diabetes or gastrointestinal diseases. Oral fluid-based biomarkers have demonstrated easy accessibility and potential as diagnostics for oral and systemic diseases, including the identification of SARS-CoV-2 in saliva. Advances in biotechnology have led to innovations in lab-on-a-chip and biosensors to interface with oral-based biomarker assessment. This review highlights new developments in oral biomarker discovery and their validation for clinical application to advance precision oral medicine through improved diagnosis, prognosis and patient stratification. Their potential to improve clinical outcomes of periodontitis and associated chronic conditions will benefit the dental and overall public health. 10.3389/fphar.2020.588480
Computational approaches to investigate the relationship between periodontitis and cardiovascular diseases for precision medicine. Human genomics Periodontitis is a highly prevalent inflammatory illness that leads to the destruction of tooth supporting tissue structures and has been associated with an increased risk of cardiovascular disease (CVD). Precision medicine, an emerging branch of medical treatment, aims can further improve current traditional treatment by personalizing care based on one's environment, genetic makeup, and lifestyle. Genomic databases have paved the way for precision medicine by elucidating the pathophysiology of complex, heritable diseases. Therefore, the investigation of novel periodontitis-linked genes associated with CVD will enhance our understanding of their linkage and related biochemical pathways for targeted therapies. In this article, we highlight possible mechanisms of actions connecting PD and CVD. Furthermore, we delve deeper into certain heritable inflammatory-associated pathways linking the two. The goal is to gather, compare, and assess high-quality scientific literature alongside genomic datasets that seek to establish a link between periodontitis and CVD. The scope is focused on the most up to date and authentic literature published within the last 10 years, indexed and available from PubMed Central, that analyzes periodontitis-associated genes linked to CVD. Based on the comparative analysis criteria, fifty-one genes associated with both periodontitis and CVD were identified and reported. The prevalence of genes associated with both CVD and periodontitis warrants investigation to assess the validity of a potential linkage between the pathophysiology of both diseases. 10.1186/s40246-024-00685-7
Pharmacogenomic landscape of head and neck squamous cell carcinoma informs precision oncology therapy. Science translational medicine Head and neck squamous cell carcinoma (HNSCC) is a common and frequently lethal cancer with few therapeutic options. In particular, there are few effective targeted therapies. Development of highly effective therapeutic strategies tailored to patients with HNSCC remains a pressing challenge. To address this, we present a pharmacogenomic study to facilitate precision treatments for patients with HNSCC. We established a large collection of 56 HNSCC patient-derived cells (PDCs), which recapitulated the molecular features of the original tumors. Pharmacological assessment of HNSCCs was conducted using a three-tiered high-throughput drug screening using 2248 compounds across these PDC models and an additional 18 immortalized cell lines. We integrated genomic, transcriptomic, and pharmacological analysis to predict biomarkers, gene-drug associations, and validated biomarkers. These results supported drug repurposing for multiple HNSCC subtypes, including the JAK2 inhibitor fedratinib, for low -expressing HNSCC cases, and the topoisomerase inhibitor mitoxantrone, for -activated HNSCC cases. Our results demonstrated concordance between susceptibility predictions from the PDCs and the matched patients' responses to standard clinical medication. Moreover, we identified and experimentally confirmed that high expression of elicited therapeutic resistance to docetaxel and high expression conferred resistance to afatinib. We further validated as a predictive biomarker for the efficacy of docetaxel therapy in a phase 2 clinical trial. In summary, our study shows that this HNSCC cell resource, as well as the resulting pharmacogenomic profiles, is effective for biomarker discovery and for guiding precision oncology therapies in HNSCCs. 10.1126/scitranslmed.abo5987
Toward the use of precision medicine for the treatment of head and neck squamous cell carcinoma. Gong Wang,Xiao Yandi,Wei Zihao,Yuan Yao,Qiu Min,Sun Chongkui,Zeng Xin,Liang Xinhua,Feng Mingye,Chen Qianming Oncotarget Precision medicine is a new strategy that aims at preventing and treating human diseases by focusing on individual variations in people's genes, environment and lifestyle. Precision medicine has been used for cancer diagnosis and treatment and shows evident clinical efficacy. Rapid developments in molecular biology, genetics and sequencing technologies, as well as computational technology, has enabled the establishment of "big data", such as the Human Genome Project, which provides a basis for precision medicine. Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with a high incidence rate and low survival rate. Current therapies are often aggressive and carry considerable side effects. Much research now indicates that precision medicine can be used for HNSCC and may achieve improved results. From this perspective, we present an overview of the current status, potential strategies, and challenges of precision medicine in HNSCC. We focus on targeted therapy based on cell the surface signaling receptors epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and human epidermal growth factor receptor-2 (HER2), and on the PI3K/AKT/mTOR, JAK/STAT3 and RAS/RAF/MEK/ERK cellular signaling pathways. Gene therapy for the treatment of HNSCC is also discussed. 10.18632/oncotarget.13798
Precision Medicine on the Effects of Microbiota on Head-Neck Diseases and Biomarkers Diagnosis. Journal of personalized medicine Precision medicine using highly precise technologies and big data has produced personalised medicine with rapid and reliable diagnoses and targeted therapies. The most recent studies have directed precision medicine into the study of tumours. The application of precision medicine in the oral microbiota can be used both in the field of prevention and treatment in the strictly dental field. This article aims to evaluate the interaction between microbiota and oral cancer and the presence of biomarkers as risk predictors. MATERIALS AND METHODS:A literature search of PubMed, Scopus, and Web of Science was performed analysing the various interactions between microorganisms, biomarkers, and oral cancer. RESULTS:After screening processes, 21 articles were selected for qualitative analysis. CONCLUSION:The correlation between oral diseases/cancers and changes in the microbiota explains the increasing utility of precision medicine in enhancing diagnosis and adapting treatment on the individual components of the microbiota. Diagnosing and treating oral diseases and cancers through precision medicine gives, as well as economic advantages to the health care system, predictable and rapid management of the patient. 10.3390/jpm13060933
Deep Machine Learning for Oral Cancer: From Precise Diagnosis to Precision Medicine. Frontiers in oral health Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide and its incidence is on the rise in many populations. The high incidence rate, late diagnosis, and improper treatment planning still form a significant concern. Diagnosis at an early-stage is important for better prognosis, treatment, and survival. Despite the recent improvement in the understanding of the molecular mechanisms, late diagnosis and approach toward precision medicine for OSCC patients remain a challenge. To enhance precision medicine, deep machine learning technique has been touted to enhance early detection, and consequently to reduce cancer-specific mortality and morbidity. This technique has been reported to have made a significant progress in data extraction and analysis of vital information in medical imaging in recent years. Therefore, it has the potential to assist in the early-stage detection of oral squamous cell carcinoma. Furthermore, automated image analysis can assist pathologists and clinicians to make an informed decision regarding cancer patients. This article discusses the technical knowledge and algorithms of deep learning for OSCC. It examines the application of deep learning technology in cancer detection, image classification, segmentation and synthesis, and treatment planning. Finally, we discuss how this technique can assist in precision medicine and the future perspective of deep learning technology in oral squamous cell carcinoma. 10.3389/froh.2021.794248
Oral Delivery of Biologics for Precision Medicine. Durán-Lobato Matilde,Niu Zhigao,Alonso María José Advanced materials (Deerfield Beach, Fla.) The emerging field of precision medicine is rapidly growing, fostered by the advances in genome mapping and molecular diagnosis. In general, the translation of these advances into precision treatments relies on the use of biological macromolecules, whose structure offers a high specificity and potency. Unfortunately, due to their complex structure and limited ability to overcome biological barriers, these macromolecules need to be administered via injection. The scientific community has devoted significant effort to making the oral administration of macromolecules plausible thanks to the implementation of drug delivery technologies. Here, an overview of the current situation and future prospects in the field of oral delivery of biologics is provided. Technologies in clinical trials, as well as recent and disruptive delivery systems proposed in the literature for local and systemic delivery of biologics including peptides, antibodies, and nucleic acids, are described. Strategies for the specific targeting of gastrointestinal regions-stomach, small bowel, and colon-cell populations, and internalization pathways, are analyzed. Finally, challenges associated with the clinical translation, future prospects, and identified opportunities for advancement in this field are also discussed. 10.1002/adma.201901935
Saliva in the diagnosis of diseases. Zhang Chen-Zi,Cheng Xing-Qun,Li Ji-Yao,Zhang Ping,Yi Ping,Xu Xin,Zhou Xue-Dong International journal of oral science Saliva is secreted from the salivary glands and has multiple functions, including mouth cleaning and protection, antibacterial effects and digestion. With the rapid advancement in salivaomics, saliva is well recognized as a pool of biological markers. Saliva, as a non-invasive and safe source, could be a substitute for blood in the diagnosis and prognosis of diseases. This review summarizes the latest advancements in saliva-related studies and addresses the potential value of saliva in the early diagnosis of oral diseases, such as dental caries and periodontal disease, as well as cancer, diabetes and other systemic disorders. Saliva biomarkers range from changes in the biochemical indices of DNA, RNA and proteins to the diversification of microbiota structures. This study integrates data reported in the recent literature and discusses the clinical significance and prospects for the application of saliva in the early diagnosis of diseases, translational medicine and precision medicine. 10.1038/ijos.2016.38
Precision Medicine in Oral Health and Diseases: A Systematic Review. Journal of personalized medicine Precision medicine (PM) is personalized medicine that can develop targeted medical therapies for the individual patient, in which "omics" sciences lead to an integration of data that leads to highly predictive models of the functioning of the individual biological system. They enable rapid diagnosis, assessment of disease dynamics, identification of targeted treatment protocols, and reduction of costs and psychological stress. "Precision dentistry" (DP) is one promising application that need further investigation; the purpose of this paper is therefore to give physicians an overview of the knowledge they need to enhance treatment planning and patient response to therapy. A systematic literature review was conducted on the PubMed, Scopus, and Web of Science databases by analyzing the articles examining the role of precision medicine in dentistry. PM aims to shed light on cancer prevention strategies, by identifying risk factors, and on malformations such as orofacial cleft. Another application is pain management by repurposing drugs created for other diseases to target biochemical mechanisms. The significant heritability of traits regulating bacterial colonization and local inflammatory responses is another result of genomic research, and is useful for DP in the field of caries and periodontitis. This approach may also be useful in the field of orthodontics and regenerative dentistry. The possibility of creating an international network of databases will lead to the diagnosis, prediction, and prevention of disease outbreaks, providing significant economic savings for the world's health care systems. 10.3390/jpm13050725
Phenotypic Subtypes of OSA: A Challenge and Opportunity for Precision Medicine. Chest Current strategies for the management of OSA reflect a one-size-fits-all approach. Diagnosis and severity of OSA are based on the apnea-hypopnea index and treatment initiated with CPAP, followed by trials of alternatives (eg, oral appliances) if CPAP "fails." This approach does not consider the heterogeneity of individuals with OSA, reflected by varying risk factors, pathophysiological causes, clinical manifestations, and consequences. Recently, studies using analytic approaches such as cluster analysis have taken advantage of this heterogeneity to identify OSA phenotypes, or subtypes of patients with unique characteristics, that may enable more personalized approaches to prognostication and treatment. Examples include symptom-based subtypes such as "excessively sleepy" and "disturbed sleep" with differing impact of CPAP on symptoms and health-related quality of life. Polysomnographic subtypes, distinguished by respiratory event association with hypoxemia, arousals, or both, exhibit varying risks of cardiovascular disease and response to therapy. This review summarizes the findings from recent cluster analysis studies in sleep apnea and synthesizes common themes to describe the potential role (and limitations) of phenotypic subtypes in precision medicine for OSA. It also highlights future directions, including linking of phenotypes to clinically relevant outcomes, rigorous and transparent assessment of phenotype reproducibility, and need for tools that categorize patients into subtypes, to prospectively validate phenotype-based prognostication and treatment approaches. Finally, we highlight the critical need to include women and more racially/ethnically diverse populations in this area of research if we are to leverage the heterogeneity of OSA to improve patient lives. 10.1016/j.chest.2019.09.002