Uncovering the functional potential of the developing peri-implant microbiome

摘要 牙齿脱落是一种令人惊讶的常见疾病，近60%的美国人年龄超过50岁， 根据NIDCR的数据，25%的19岁以上的人失去了10颗以上的牙齿。这代表了数百万 咀嚼功能、语音能力和审美能力受损的人。在过去的几十年里， 骨整合种植体支持的骨重建已经发展成为一种通常更好的替代方法， 传统的活动假牙或固定桥。每年有近200万颗牙齿植入， 预计每年增长15%，牙科植入物已成为一种广为接受的治疗方式， 恢复形式和功能。 虽然骨内植入物已被证明是高度可靠的，并提供了比替代品更多的功能， 成功取决于周围健康组织的维持。不幸的是，两个微生物驱动的 炎性疾病通常伴随这些炎症：种植体周围粘膜炎（影响50%的种植体 80%的患者）和种植体周围炎（20%的患者中10%的种植体）。临床上，虽然这些条件 分别模拟牙龈炎和牙周炎，并已进行治疗，治疗结果 但复发率高得令人不安。此外，临床研究不仅关注 主要是在疾病的研究中，调查仅检查了微生物群落组成， 直到最近，一直使用范围有限的工具来处理。 在这里，我们提出了第一个纵向高通量，开放式的宏基因组学研究的健康人， 植入微生物组的目的如下：确定细菌功能的形成至关重要的微生物， 植入微生物组，在功能宏基因组中研究微生物储库假说的有效性 水平，并测量种植体周围和牙周定植动力学之间的一致性。 这些研究代表了以关键发现为中心的检查，旨在建立基本的 健康的性质和参与重要临床环境的整体功能途径， 全球数百万患者。随着他们的完成，我们预计将建立一个关键的图书馆， 发育标记物在新生植入物周围宏基因组发育的关键点，以及它们如何 不同于健康牙周宏基因组的群落和功能组成。这些将作为 为未来研究潜在的治疗靶点和生物标志物奠定了基础， 敏感、个性化的护理选择，最终将改善当前的临床结果。

Abstract Tooth loss is a surprisingly common condition with nearly 60% of Americans over the age of 50 and more than 25% over the age of 19 missing more than 10 teeth, according to the NIDCR. This represents millions of people with impaired masticatory function, phonetic ability, and aesthetics. In the last few decades, osseointegrated implant supported restorations have developed into an often-superior alternative to the traditional removable dentures or fixed bridges. With nearly 2 million dental implants placed each year, and projected increases of 15% annually, dental implants have emerged as a well-accepted treatment modality to restore form and function. While endosseous implants have proven highly reliable and provide increased function over alternatives, their success is dependent on maintenance of the surrounding healthy tissue. Unfortunately, two microbially driven inflammatory diseases often accompany these restorations: Peri-implant mucositis (affecting 50% of implants in 80% of patients) and peri-implantitis (10% of implants in 20% of patients). Clinically, while these conditions mimic gingivitis and periodontitis respectively and have been treated as such, outcomes of therapies have been modest with disturbingly high rates of recurrence. Furthermore, not only has clinical research focused primarily on studies of disease, investigations have examined microbial community composition alone and, until recently, been approached using tools of limited scope. Here we propose the first longitudinal high-throughput, open-ended metagenomics study of the healthy peri- implant microbiome with the following aims: Identifying bacterial functions critical to the formation of the peri- implant microbiome, investigating the validity of the microbial reservoir hypothesis at a functional metagenomic level, and measuring congruence between peri-implant and periodontal colonization dynamics. These studies represent critical discovery-centered examinations targeted at establishing the essential properties of health and the integral functional pathways involved in an important clinical environment affecting millions of patients worldwide. With their completion, we expect to have established a library of critical development markers at key points in the development of the nascent peri-implant metagenome and how they differ from the community and functional makeup of the healthy periodontal metagenome. These will serve as the basis for future investigations into potential therapeutic targets and biomarkers, enabling the development of sensitive, personalized care options that will ultimately improve on current clinical outcomes.