The microbiology lab led by ADA Forsyth faculty members Jessica Mark Welch, Ph.D., and Gary Borisy, Ph.D., takes genomic analysis to a new level through an innovative bioinformatics approach known as metapangenomics.
Building on ADA Forsyth’s pioneering work in cataloging the oral microbiome, the AFI research team has now advanced the field by creating highly detailed profiles of the oral microbiome. Their approach enables them to map not only the genetic composition of individual species but also their habitat preferences and patterns of gene expression within complex microbial communities.
Metapangenomics combines two sets of analysis techniques – metagenomics and pangenomics. Metagenomics sequences all DNA from a given microbial community, capturing the full range of organisms present in a sample. Pangenomics, on the other hand, focuses on a single bacterial species or group, exploring the complete genetic diversity across its different strains. By integrating these methods, metapangenomics allows scientists to study not only which microbes are present, but also how genetic variation within individual species shapes their behavior, ecological roles, and potential impact on health and disease.
ADA Forsyth postdoctoral fellow Jonathan Giacomini, Ph.D., explains why this innovative, multi-omic approach is more than just the sum of its parts: “Metapangenomics helps unravel the complex web of microbial interactions in the oral microbiome. With increased context surrounding microbial interactions, we can form hypotheses and work to confirm ideas about what constitutes a healthy oral microbiome.
“We can start answering bigger questions, like, how do they interact? What roles do specific genes play in their survival and function?”
Dr. Giacomini is the first author of the researchers’ latest study, published in the journal Microbiology Spectrum. Drs. Giacomini, Mark Welch, and Borisy collaborated on the study with AFI’s Professor Emeritus Floyd Dewhirst, D.D.S, Ph.D., and Julian Torres-Morales, M.S. They performed metapangenomic analysis using the Anvi’o platform.
Now empowered to craft a full picture of the genetic potential within a microbial community, the scientists’ observations about the ecology of bacteria in the mouth lead them closer to new ideas for diagnostic, therapeutic, or preventive strategies related to oral and overall health.
In the paper, the researchers examined bacteria species in the Neisseriaceae family, including genera that are abundant and important in the mouth, such as Neisseria, Eikenella, Kingella, and Simonsiella. It is the fifth paper in a series of genomic analyses, each examining a different family of bacteria.
The team noted the habitat preferences of each species, with different sets of species dwelling on the top of the tongue, on the surface of the cheeks, or within supragingival plaque on the surface of the teeth. Metapangenomic analysis of the microbes’ genetic makeup led the authors to new evidence about their metabolic actions, interactions in the ecosystem, and other functions.
The nitrate-processing role of Neisseriaceae species highlights a larger question that microbiologists are striving to answer more precisely: how specific bacterial functions within complex microbial communities influence cardiovascular and neural health.
Scientific literature suggests certain species of oral bacteria are key players in nitrate reduction into nitrite. However, this study presents new possibilities for identifying additional bacteria which may play just as important a role in nitrate reduction as those presently considered key players.
Stronger insights into this metabolic pathway and many others allow scientists to determine which bacteria are driving the action in the oral microbiome that ultimately influences systemic health. These processes include the spread or mitigation of disease, absorption of nutrients, and symbiotic relationships between bacterial species.
“These papers are hypothesis generators,” Dr. Giacomini said. “We’re going group by group, mining data, and creating a clearer picture of who’s who in the mouth, and which genes are shaping their characteristics. From there, we can design experiments.”
Pictured: The microbes in yellow belong to the Neisseriaceae in the fluorescent image created at ADA Forsyth’s microscopy lab.
