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.
Peri-implantitis, a microbially driven disease, is the single major cause of endosseous dental implant loss; affecting 10% of implants and 20% of patients. With more than 500,000 implants being placed each year and an upward trajectory, this disease that has the potential to develop into an explosive public health issue. Unfortunately, therapeutic outcomes have been modest, with disturbingly high rates of disease recurrence. Currently peri-implantitis is generally treated using therapies designed for periodontitis, indicating that the peri- implant environment may exhibit critical differences from the periodontal environment. While recent studies have begun investigating this idea at the microbiome level, they have been limited to surveys of organismal composition, and have used disease as starting point instead of health. Here we propose to carry out the first longitudinal, open-ended whole metagenome survey of the healthy peri-implant microbiome in comparison to the periodontal microbiome. This will establish a temporal library of metagenomic transitions in functional potential, in addition to species composition, from the initial colonization of new implants through to establishment of a healthy microbiome. Ultimately this novel characterization will open pathways for more effective studies of prevention and development of more effective and personalized therapies.
