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情况，近60%的50岁以上的美国人 根据NIDCR的数据，19岁以上的人中有25%的人缺牙超过10颗。这代表着数百万人 咀嚼功能受损的人，发音能力和审美能力受损。在过去的几十年里， 骨结合种植体支持的修复已经发展成为一种往往更好的替代 传统的活动义齿或固定桥。每年有近200万颗牙种植体， 预计每年将增长15%，种植牙齿已成为一种被广泛接受的治疗方式 恢复形式和功能。 虽然骨内植入物已被证明高度可靠，并提供了比替代方案更好的功能，但他们的 成功依赖于周围健康组织的维护。不幸的是，两种微生物驱动 炎症性疾病通常伴随着这些修复体：种植体周围粘膜炎(影响50%的种植体 在80%的患者中)和种植体周围炎(20%的患者中有10%的种植者)。在临床上，虽然这些情况 分别模拟牙周炎和牙周炎，并按此进行治疗，治疗结果如下 一直保持温和，复发率高得令人不安。此外，不仅临床研究专注于 主要是关于疾病的研究，调查只检查了微生物群落的组成， 直到最近，还在使用范围有限的工具与之接洽。 在这里，我们提出了第一个纵向高通量，开放的元基因组学研究的健康周。 植入微生物组，目标如下：鉴定对形成周围炎至关重要的细菌功能-- 植入微生物组，在功能元基因组中调查微生物储存库假说的有效性 水平，并测量种植体周围和牙周定植动力学之间的一致性。 这些研究代表了以发现为中心的关键检查，旨在确定 健康的特性和影响重要临床环境的整体功能通路 全球数以百万计的患者。随着它们的完成，我们预计将建立一个关键的库 在新生种植体周围元基因组发育的关键点上的发育标志物及其如何 有别于社区和功能组成的健康的牙周元基因组。这些将作为 为未来研究潜在的治疗靶点和生物标记物奠定基础，使开发成为可能 敏感的、个性化的护理选项，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.