The oral‐systemic personalized medicine model at Marshfield Clinic

Oral Diseases (2012) 19 , 1–17 Periodontal disease and diabetes, two diseases that have achieved epidemic status, share a bidirectional relationship driven by micro‐inflammatory processes. The present review frames the current understanding of the pathological processes that appear to link these diseases and advances the hypothesis that reversal of the epidemic is possible through application of interdisciplinary intervention and advancement of oral‐systemic personalized medicine. An overview of how Marshfield Clinic’s unique clinical, informatics and bio‐repository resources and infrastructures are being aligned to advance oral‐systemic personalized medicine is presented as an interventional model with the potential to reverse the epidemic trends seen for these two chronic diseases over the past several decades. The overall vision is to engineer a transformational shift in paradigm from ‘personalized medicine’ to ‘personalized health’.     

人体微生物组在辅助2型糖尿病诊疗中的潜在应用

人体微生物组是指人体体表及内部的微生物的遗传信息总和,与人类健康与疾病状态存在密切关系。口腔和肠道微生物是最具多样化的微生物群落,两者可以交互影响,在疾病发生发展过程中共同发挥作用,并可以实时反映机体的健康与疾病状态。2型糖尿病是由遗传和环境因素引起的代谢紊乱,最近的研究指出微生物与糖尿病存在关联。本文结合近期的研究进展,就2型糖尿病患者口腔微生物和肠道微生物的特征进行综述,有望为探索基于微生物组特征的2型糖尿病风险预测、诊断和预后预测的疾病模型的建立提供参考依据。     

人体微生物组在辅助2型糖尿病诊疗中的潜在应用

人体微生物组是指人体体表及内部的微生物的遗传信息总和,与人类健康与疾病状态存在密切关系。口腔和肠道微生物是最具多样化的微生物群落,两者可以交互影响,在疾病发生发展过程中共同发挥作用,并可以实时反映机体的健康与疾病状态。2型糖尿病是由遗传和环境因素引起的代谢紊乱,最近的研究指出微生物与糖尿病存在关联。本文结合近期的研究进展,就2型糖尿病患者口腔微生物和肠道微生物的特征进行综述,有望为探索基于微生物组特征的2型糖尿病风险预测、诊断和预后预测的疾病模型的建立提供参考依据。     

人体口腔微生物宏基因组的研究进展

人体生态环境中共生着数量庞大的微生物群落,被誉为人体第二基因组。口腔微生物与口腔及全身的健康和疾病有着密切的联系,新一代高通量基因芯片和第二代测序技术的涌现让人们对口腔微生物有了更全面的了解。本文就微生物宏基因组研究技术、口腔微生物宏基因组及其与口腔和全身疾病防治的最新进展进行综述。     

A practical guide to the oral microbiome and its relation to health and disease

The oral microbiome is incredibly complex with the average adult harboring about 50–100 billion bacteria in the oral cavity, which represent about 200 predominant bacterial species. Collectively, there are approximately 700 predominant taxa of which less than one‐third still have not yet been grown in vitro. Compared to other body sites, the oral microbiome is unique and readily accessible. There is extensive literature available describing the oral microbiome and discussing the roles that bacteria may play in oral health and disease. However, the purpose of this review is not to rehash these detailed studies but rather to educate the reader with understanding the essence of the oral microbiome, namely that there are abundant bacteria in numbers and types, that there are molecular methods to rapidly determine bacterial associations, that there is site specificity for colonization of the host, that there are specific associations with oral health and disease, that oral bacteria may serve as biomarkers for non‐oral diseases, and that oral microbial profiles may have potential use to assess disease risk.     

Periodontal disease and systemic conditions: a bidirectional relationship

For decades, physicians and dentists have paid close attention to their own respective fields, specializing in medicine pertaining to the body and the oral cavity, respectively. However, recent findings have strongly suggested that oral health may be indicative of systemic health. Currently, this gap between allopathic medicine and dental medicine is quickly closing, due to significant findings supporting the association between periodontal disease and systemic conditions such as cardiovascular disease, type 2 diabetes mellitus, adverse pregnancy outcomes, and osteoporosis. Significant effort has brought numerous advances in revealing the etiological and pathological links between this chronic inflammatory dental disease and these other conditions. Therefore, there is reason to hope that the strong evidence from these studies may guide researchers towards greatly improved treatment of periodontal infection that would also ameliorate these systemic illnesses. Hence, researchers must continue not only to uncover more information about the correlations between periodontal and systemic diseases but also to focus on positive associations that may result from treating periodontal disease as a means of ameliorating systemic diseases.     

Interactions between sleep disorders and oral diseases

Dental sleep medicine is a rapidly growing field that is in close and direct interaction with sleep medicine and comprises many aspects of human health. As a result, dentists who encounter sleep health and sleep disorders may work with clinicians from many other disciplines and specialties. The main sleep and oral health issues that are covered in this review are obstructive sleep apnea, chronic mouth breathing, sleep‐related gastroesophageal reflux, and sleep bruxism. In addition, edentulism and its impact on sleep disorders are discussed. Improving sleep quality and sleep characteristics, oral health, and oral function involves both pathophysiology and disease management. The multiple interactions between oral health and sleep underscore the need for an interdisciplinary clinical team to manage oral health‐related sleep disorders that are commonly seen in dental practice.     

口腔微生物群落结构的影响因素

口腔微生物群落作为人体最多样化的微生物群落之一,其生态失衡不仅可以诱发多种口腔疾病,如龋病、牙髓根尖周病、牙周病等,还与心血管疾病、糖尿病等多种系统性疾病紧密相关。口腔微生物群落结构受多种因素影响,本文就口腔微生物群落结构的影响因素作一综述,文献复习结果表明:环境因素在口腔微生物群落的塑造中起重要作用,而遗传和饮食因素的影响目前尚有争议;此外,系统性疾病也可能影响口腔微生物群落结构。目前,高通量测序研究已确定一些“核心微生物群”,不同环境、不同遗传背景下的“核心微生物群”将是下一步的研究方向。     

World Workshop on Oral Medicine VII: Targeting the microbiome for oral medicine specialists—Part 1. A methodological guide

Advances in high‐throughput sequencing technologies have allowed for a rapid increase in knowledge about the human microbiome in both healthy and diseased states, which is expected to increase our understanding of multifactorial diseases. The World Workshop on Oral Medicine VII chose the microbiome as one of its topics of focus. Part 1 of this review provides updated knowledge in the field of microbiome research, describes the advantages and disadvantages of currently available sequencing technologies, and proposes a seven‐step “recipe” for designing and performing studies that is supported by contemporary evidence. Part 2 of this review in a companion paper discusses the results of high‐throughput sequencing studies published to date on the microbiota associated with oral mucosal diseases. The goal of this collective enterprise is to encourage more oral medicine specialists to become engaged in multidisciplinary collaborations to investigate the role of the microbiome in relation to oral diseases, which could potentially lead to enhanced diagnosis, risk assessment and treatment of these patients.     

口腔微生物群落在口腔与全身疾病预警中的作用

口腔微生物群落是指定植于人体口腔的微生物集合,多以生物膜形式行使微生物生理学功能。当微生物群落与宿主间生态关系失衡时,可诱发多种口腔感染性疾病,包括龋病、牙髓根尖周病、牙周病、智齿冠周炎、颌骨骨髓炎等,严重危害口腔健康。更为重要的是,口腔微生物群落与口腔肿瘤、糖尿病、类风湿性关节炎、心血管疾病及早产等系统性疾病紧密相关,口腔微生物群落结构特征可作为口腔及全身健康预警的重要标记。随着“人类微生物组计划”及其他微生物宏基因组学相关项目的开展,人们对口腔微生物群落的认识不断深入,已获得了海量大数据信息。在“后微生物组计划”时代如何有效地将微生物群落大数据转化为具有实际运用价值的临床诊疗手段,进而为患者提供有效的个体化医疗服务将是推动口腔疾病乃至全身疾病“精准医疗”的重大前沿问题。本文拟从常见口腔及相关系统性疾病微生物群落研究进展入手,阐述口腔微生物群落信息在疾病发生、发展及预后预警中的作用,提出建立基于口腔微生物群落疾病预警系统的必要性,为实现口腔疾病及相关系统性疾病的个性化诊疗提供新的思路。     

Relationship between the oral cavity and cardiovascular diseases and metabolic syndrome

The components of the human body are closely interdependent; as a result, disease conditions in some organs or components can influence the development of disease in other body locations. The effect of oral health upon health in general has been investigated for decades by many epidemiological studies. In this context, there appears to be a clear relationship between deficient oral hygiene and different systemic disorders such as cardiovascular disease and metabolic syndrome. The precise relationship between them is the subject of ongoing research, and a variety of theories have been proposed, though most of them postulate the mediation of an inflammatory response. This association between the oral cavity and disease in general requires further study, and health professionals should be made aware of the importance of adopting measures destined to promote correct oral health. The present study conducts a Medline search with the purpose of offering an update on the relationship between oral diseases and cardiovascular diseases, together with an evaluation of the bidirectional relationship between metabolic syndrome and periodontal disease. Most authors effectively describe a moderate association between the oral cavity and cardiovascular diseases, though they also report a lack of scientific evidence that oral alterations constitute an independent cause of cardiovascular diseases, or that their adequate treatment can contribute to prevent such diseases. In the case of metabolic syndrome, obesity and particularly diabetes mellitus may be associated to an increased susceptibility to periodontitis. However, it is not clear whether periodontal treatment is able to improve the systemic conditions of these patients. Key words:Cardiovascular diseases, periodontitis, metabolic syndrome, obesity, diabetes mellitus.     

Microbiological changes of the ageing oral cavity

ObjectiveAgeing is a physiological process that affects virtually all systems of the human body. Age-associated changes in the oral cavity reflect changes in the composition of its microbial inhabitants, which can be compatible with health or form dysbiotic communities that favor the establishment of disease. This paper focuses on discussing such age-driven changes of the oral microbiome, as well as their association with common oral infectious diseases, including dental caries, periodontitis, peri-implantitis and oral candidiasis.DesignThis is a comprehensive narrative review of the literature.ResultsThe oropharyngeal microbiome of elderly individuals may foster a number of microorganisms such as enterobacteria, pseudomonads, staphylococci and yeasts that can become opportunistic pathogens in elderly individuals with weakened immunity or deteriorated general health. No considerable microbiological variations are noted with regards to common oral diseases, such as dental caries and periodontitis, between younger and elderly populations, whereas an increase in the prevalence of oral actinomycetes is noted by ageing.ConclusionsWhether naturally occurring or driven by underlying disease, the ecology of oral cavity is dynamically modified over time, eliciting changes in the composition of the resident oral microbiome.     

Host Genome,Epigenome, and Oral Microbiome Interactions: Toward Personalized Periodontal Therapy

Periodontal diseases are multidimensional and complex. Bacterial content is the initiator, but disease progression depends on genetic and environmental parameters related to the host. Although bone loss magnitude is the common resulting outcome, the biologic process likely represents a unique inflammatory response characteristic to every individual. Therefore, it is obvious that practitioners must take into account the influence of these parameters and tailor a treatment accordingly. New, emerging deoxyribonucleotide‐based technologies allow integration of the biologic impact of the environment, and periodontists should be prepared to incorporate these technologies into their practice to advance personalized medicine. This commentary provides updated insights on the distinctiveness of inflammation per individual in terms of microbiome and genome specificity and cites some educational resources helpful for implementing individualized therapy.     

Microbial protection and virulence in periodontal tissue as a function of polymicrobial communities: symbiosis and dysbiosis

This review discusses polymicrobial interactions with the host in both health and disease. As our ability to identify specific bacterial clonal types, with respect to their abundance and location in the oral biofilm, improves, we will learn more concerning their contribution to both oral health and disease. Recent studies examining host– bacteria interactions have revealed that commensal bacteria not only protect the host simply by niche occupation, but that bacterial interactions with host tissue can promote the development of proper tissue structure and function. These data indicate that our host‐associated polymicrobial communities, such as those found in the oral cavity, co‐evolved with us and have become an integral part of who we are. Understanding the microbial community factors that underpin the associations with host tissue that contribute to periodontal health may also reveal how dysbiotic periodontopathic oral communities disrupt normal periodontal tissue functions in disease. A disruption of the oral microbial community creates dysbiosis, either by overgrowth of specific or nonspecific microorganisms or by changes in the local host response where the community can now support a disease state. Dysbiosis provides the link between systemic changes (e.g. diabetes) and exogenous risk factors (e.g. smoking), and the dysbiotic community, and can drive the destruction of periodontal tissue. Many other risk factors associated with periodontal disease, such as stress, aging and genetics, are also likely to affect the microbial community, and more research is needed, utilizing sophisticated bacterial taxonomic techniques, to elucidate these effects on the microbiome and to develop strategies to target the dysbiotic mechanisms and improve periodontal health.     

Oral-lung microbiome interactions in lung diseases

The proximity and continuity of the oral cavity and the lower respiratory tract allows the oropharyngeal microbiome to be a major determinant of the lung microbiome. In addition, host-pathogen interactions related to the oropharyngeal microbiome or its metabolites could propagate systemic inflammation or modulate host defense mechanisms that could affect other organs, including the lung. There is increasing appreciation of the pathophysiologic significance of the lung microbiome, not only in the classical infection-related diseases, pneumonia, bronchiectasis, and cystic fibrosis, but also in chronic noninfectious lung diseases, such as chronic obstructive pulmonary disease, asthma, and pulmonary fibrosis. In this review, we will explore the relationship of the oral microbiome with lung diseases, such as pneumonia, chronic obstructive pulmonary disease, asthma, and cystic fibrosis.     

Biodiversity of the human oral mycobiome in health and disease

The organisms that colonize the human body over a lifetime are diverse, extensive and gargantuan. A fair proportion of the microbiota that constitutes this human microbiome live within our oral cavities mostly as harmonious associates causing only sporadic disease. An important core constituent of the microbiome is the mycobiome, representing various fungal genera. Up until recently, only a few species of fungi, mainly Candida species, were thought to constitute the human oral mycobiome. The reasons for this are manifold, although the uncultivable nature of many fungi in conventional laboratory media, and their complex genetic composition seem to be the major factors which eluded their detection over the years. Nevertheless, recent advances in computing and high‐throughput sequencing such as next‐generation sequencing (NGS) platforms have provided us a panoramic view of a totally new world of fungi that are human oral cohabitués. Their diversity is perplexing, and functionality yet to be deciphered. Here, we provide a glimpse of what is currently known of the oral mycobiome, in health and disease, with some future perspectives.