The Role of Genetics in the Human Microbiome
The Human Microbiome Project has revealed much about normal bacteria in the mouth and other body sites. But how these bacteria are acquired and how long they stay around is less understood. Recent studies tracking bacteria in non-oral body sites have demonstrated that strains of bacteria can persist in humans over long periods of time. Thus, it is likely that early exposures to bacteria may have important, long-lasting implications for disease and health.
This potential determinant of oral health will be investigated by Ann Griffen DDS, MS, Professor in the Division of Pediatric Dentistry and the Division of Biosciences, and her collaborator and husband, Gene Leys PhD, Professor in the Division of Biosciences. In May 2014, they were awarded a five—year grant for $1,923,960 to investigate the initial acquisition of the human oral microbiome by The National Institute of Dental and Craniofacial Research (NIDCR), the federal government's lead agency for scientific research on oral, dental, and craniofacial health and disease. NIDCR is one of the National Institutes of Health (NIH) in the U.S. Department of Health and Human Services.
Their preliminary studies on the initial acquisition and assembly of the oral microbiome using next generation sequencing of the 16S rRNA gene showed a remarkably robust and specific acquisition of a core microbiota. Humans share a common core of bacteria, with less than 1000 species as regular residents in the oral cavities of the human population. Most 1-year-old children harbor about 50 species in their mouths, while adults typically have around 200. The major species are common to everyone, and children harbor a subset of the bacteria found in adults. In this new study, the research team will follow children to young adulthood to track the development of mature adult oral microbial communities.
"This study can potentially lead to future therapeutic protocols, where a genetic match for a person's oral microbiome, including bacterial surface receptors, can become a supplement used to bring that person back to normal oral health."
The robust assembly of a small, shared community of oral organisms in infants is truly remarkable when we consider the vast range of bacteria to which the human oral cavity is exposed. These include bacteria that inhabit other body sites of humans, bacteria in water from environmental sources, plant foods that harbor their own microbial communities as well as soil and water bacteria, pets and animal food sources that have their own distinct microbiota, and other objects a child might encounter in oral explorations. Despite this exposure, only a limited and highly specific community of bacteria establishes in the human oral cavity, and it is similar across children. This exclusion of most species and support for a core of commensal species occurs by largely unknown mechanisms.
"This study can potentially lead to future therapeutic protocols, where a genetic match for a person's oral microbiome, including bacterial surface receptors, can become a supplement used to bring that person back to normal oral health. The process will have some similarities to organ transplant matching," says Dr. Griffen.The Griffen Leys lab will determine whether genetics plays a role in the ease of acquisition and stability of oral microbial communities. To do this, the researchers will compare how well microbial profiles match in biologic mother—child pairs and mothers and children who are adopted at birth. They will try to determine whether each human harbors a set of strains/species that is particularly well-adapted to his or her specific host environment (genetics), and whether these bacteria are a better fit for genetic offspring than those harbored by unrelated individuals. If so, the human microbiome might be another form of heritable genetic material passed from parent to offspring—another sort of "epigenetic" inheritance. To what extent the human oral microbiome is a heritable feature and to what extent it is stable over time, similar to our human genome, has major implications for disease and health.
Collaborators include Cliff Beall PhD, Research Assistant Professor, Biosciences, who is the bioinformaticist handling the gene sequencing, and Christina Igboin PhD, Research Scientist, Biosciences, who is coordinating the clinical adoption studies.