Hundreds of species of bacteria live in the human mouth, and this oral microbiome impacts human health and disease not only in the mouth but throughout the body. Some of these bacteria have been studied for decades. For others, surprisingly little is known about what roles they play in the ecology of the mouth or even where in the mouth they live. The goal of Jessica Mark Welch’s research group is to understand the structure and function of bacterial communities in the mouth, to learn how the members of the community work together, how they impact human health, and potentially, how the properties of the community can be manipulated to benefit human health.
Dr. Mark Welch and her team use both imaging and DNA sequencing approaches to investigate the structure and organization of the oral microbiome. She and her colleague Gary Borisy, also at the Forsyth Institute, developed a method called CLASI-FISH for imaging and identifying many types of bacterial cells simultaneously. Using CLASI-FISH on samples of dental plaque, they discovered highly organized, complex structures that they called “hedgehogs” because of the spiny appearance of the structures’ characteristic clusters of bacterial filaments. Using CLASI-FISH on samples scraped from the tongue, they discovered entirely different but equally complex bacterial consortia that Dr. Mark Welch calls “bacterial high-rises, little microbial apartment buildings that these bacteria build on your tongue”.
CLASI-FISH shows how the bacteria in the mouth are organized, identifying the bacteria to the level of genus or species. To find out what the species identification means – what genes the bacteria have, and what functions they encode – Dr. Mark Welch and her colleagues at the Forsyth use DNA sequencing approaches. Using the software environment Anvi’o, they construct pangenomes for groups of bacteria to discover which genes are “core,” found in every member of the group, and which genes are “accessory” or optional. They then examine metagenome data from the mouth and compare it to the pangenome to create a “metapangenome” showing which bacteria live in different people and different parts of the mouth, and what genes these bacteria have. They hope to learn why different bacteria live where they do, and how we can encourage the growth of health-promoting bacteria in the mouth.
Dr. Mark Welch also curates the Human Oral Microbiome Database, together with Forsyth colleagues Floyd Dewhirst and Tsute (George) Chen. This database provides oral microbiome researchers with high-quality, curated information about oral bacteria, their genomes, and their distribution throughout the mouth. More than two-thirds of oral bacterial species can be cultivated, but some are still “uncultivable” and Dr. Mark Welch and her team are working to cultivate these not-yet-cultivated bacteria and sequence their genomes to broaden and deepen the genomic information available for the oral microbiome.