The oral microbiome and precision medicine: A peek into the future of periodontal diagnostics

Have you ever considered that we as humans comprise approximately 23,000 genes? Most of us may have also assumed that we are living alone in our bodies, yet scientists have recently identified over 3.3 million genes that make up the human gut microbiome.¹ In fact, microbes in our body outnumber our human cells by a ratio of 10 to 1. Thus, we are not alone, and at times we may even wonder who is really in charge!

In 2008, the US National Institutes of Health (NIH) began “The Human Microbiome Project,” a massive international initiative that has now entered phase 2, known as the “Integrative Human Microbiome Project.”² The Canadian Institutes of Health Research (CIHR) oversees Canada’s strong presence in this field, serving on the steering committee of the International Human Microbiome Consortium, which coordinates human microbiome research and the sharing of data around the world. These global efforts are helping scientists and clinicians better understand how the human microbiome and its interactions with the human immune system either protect or harm the host. This information presents a more realistic view of the microbiomes found in the human body and will one day allow clinicians to focus their efforts when treating their patients.

There are 2 components to the human microbiome: a “core” and a “variable” part. The core is shared among all humans, while the variable microbiome is exclusive to each individual based on their phenotype, genotype, and unique lifestyle. The differences in species and strains of this variable portion of the microbiome among individuals may be as unique as their fingerprint!

Salme E Lavigne

Microbes do not typically occur in nature as a pure culture of a single species, but rather exist in a community of microbes, which are referred to collectively as a microbiome. In the human host, a microbiome exists in several anatomical niches, each with its own exclusive metagenome, e.g. hair, skin, gastrointestinal tract, urogenital tract, vagina, nasal and paranasal sinuses, and the oral cavity . In ideal conditions, these microbiome niches represent a species-balanced community that is important for the maintenance of human health. Each microbial inhabitant within the community maintains a unique ecosystem that is geared towards “symbiotic” interactions among the various microbes within that particular ecosystem, including the host. However, when conditions are not ideal and the niche becomes unbalanced, these communities are said to be in a state of “dysbiosis,” leading to disease.

If we translate this information to the oral cavity, this state of dysbiosis explains how oral diseases occur, particularly periodontitis. The oral cavity houses the second largest number of microbiota next to the gastrointestinal tract. Thus, the NIH-funded project has now developed organ-specific microbial databases for both the human intestinal tract and the human oral microbiome. You will find the Human Oral Microbiome Database (HOMD) online at http://www.homd.org. To date, almost 800 specific oral species have been added to the oral microbiome database but well over 1,000 are suspected to exist.

This knowledge has created a major paradigm shift in the etiology of periodontal diseases. What is now considered old knowledge is that specific “virulent” periodontal pathogens cause periodontal tissue breakdown (mainly Gram-negative anaerobic bacteria). The problem with this theory is that no specific bacteria have ever been shown to be solely causative of periodontal disease. Thus, the new theory is that disease severity is dependent upon the microbe–host environment. Periodontal breakdown in susceptible individuals creates an environment suitable for particular microbes, which then flourish. Highly associated microorganisms of the mouth appear sequentially and maintain homeostasis to keep the mouth healthy. However, interference with this symbiotic state leads to dysbiosis resulting in periodontal disease.

With this major shift in thinking, an emerging approach for disease treatment and prevention that takes into account the variability in genes, environment, and lifestyle for each person has been created, called “precision medicine.” Some of you may have heard of “personalized medicine,” which is an older term with a similar meaning. There was, however, concern that the word “personalized” could be misinterpreted to imply that treatments and preventions are being developed uniquely for each individual. In precision medicine, the focus is on identifying approaches that will be effective for groups of patients based on their common genetic, environmental, and lifestyle factors. This is in contrast to the “one size fits all” approach that has dominated medicine for decades. Thus, the preferred term today is precision medicine.

Commercialization of the human microbiome as a drug therapy has already begun. In 2013, patients infected with C. difficile were successfully treated by duodenal infusion of the fecal microbiota of a healthy individual.³ The ability to use patients’ genetic and other molecular information as part of routine medical and perhaps dental care may soon be a reality! With these new discoveries in metagenomics and microbiomics, there will be improved ability to predict which treatments will work best for specific patients. Additionally, there will be better understanding of the underlying mechanisms by which various diseases occur leading to improved approaches to preventing, diagnosing, and treating a wide range of diseases.

Because each individual harbors a unique microbiome that plays a key role in the etiology of disease within the body, periodontal disease may manifest and progress differently in different individuals, making precision medicine imperative for optimal oral health care. Indeed, the movement towards precision medicine within our own profession is well underway with the newly introduced classification system for periodontal and peri-implant diseases developed by the American Academy of Periodontology (AAP) and the European Federation of Periodontology (EFP). The new classification system, which is based on the oncology system of staging and grading, individualizes the diagnosis and the case definition of a periodontitis client, aligning it with the principles of precision medicine. This approach takes into account the multifactorial etiology of the disease, the level of complexity of its management, as well as the risk for disease recurrence, all of which facilitate optimal care and improve disease prognosis. The future of periodontal diagnostics and treatment, thanks to the emergence of precision medicine, is promising!

The only true wisdom is in knowing you know nothing,

—Socrates