"Microbes not only provide functions that promote health, but may actually guide the stages of our own immune system development," said Relman. "It seems reasonable to propose that only until we have an idea of the make-up and variability of the microbial ecosystems living within us do we begin to get an idea of the mechanisms underlying the functions they perform, such as immune system maturation and defense against pathogens."
Relman will present an overview of his lab's work on this subject, along with some new findings Feb. 16 as part of the "Innate Immunity and Oral Health" program at the annual meeting of the American Association for the Advancement of Science in Seattle.
The mouth provides a thriving community of microbes and a unique field in which to study how these tiny creatures interact with their hosts. Relman's group has concentrated efforts on the subgingival crevice - the deep gap between the gums and teeth - in their search for microbes. Even though almost 500 bacterial strains or species have been identified in this oral pocket, Relman believes there remains a substantial amount to be learned about their behavior and response to perturbation, such as brushing and flossing, and environmental insults such as being attacked by the immune system.
Some of the most basic kinds of questions remain unanswered in the microbial world, said Relman. While there is a general consensus that bacteria play a role in causing gum disease, no single microbe has been implicated as the culprit. "The details on how oral microbes cause disease is probably not a simple story," said Relman. "One agent does not equal one disease. There are complex interactions between members of the oral flora."
In its quest to sort through the interactions, Relman's group uses several unique approaches, one of which involves directly analyzing the microbes in plaque surrounding the tooth rather than growing the microbes in the lab. Previously, Relman said, the search for pathogens has been limited to things that could be cultivated, which may represent only half of the members of the oral microbial world.
By preparing DNA directly from the plaque and studying each bacterial genetic sequence, they have found microbes never before located in the mouth; some of these microbes hadn't been seen anywhere. The group is also expecting to publish a study soon on organisms previously not known to play a role in human disease.
Relman's lab is collaborating with biochemistry professor and Howard Hughes Medical Institute investigator Patrick Brown, MD, PhD, on developing microarrays - glass slides carrying thousands of DNA spots, each representing a different gene - to screen samples for thousands of micro-organisms at once. The hope is to discover the relationship between human gene expression in subgingival tissue and the microbial life found at the same time and site.
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