Jeffrey Becker

UTK microbiology

At this very second, trillions of microorganisms inhabit your mouth, gastrointestinal tract, and all other body cavities and surfaces. In fact, these bacteria, fungi, and other tiny life forms outnumber the cells of the human body ten to one, which means a substantial portion of “us” is not really us at all.

Scientists have always assumed that this diverse collection of microorganisms—termed the microbiome—intimately influences the health and well being of its mammalian host; but until just a few years ago, no one even knew how many different organisms shared our bodies, much less what they were doing there.

This is changing due to powerful new DNA sequencing technologies that analyze DNA from mixed population samples without the need to culture individual organisms—referred to as metagenomics.

JDRD Project: Survey of fungal component of the gut microbiome;
LDRD Project: Host genetic diversity as a variable selection environment for the gut microbiome, Elissa J. Chesler.

Using the mouse as a model system, JDRD team leader Jeff Becker and research professor Melinda Hauser take a metagenomic approach to cataloging the fungal diversity in a region of the large intestine known as the cecum, a site selected based on its role in gastrointestinal disease in humans.

Their work complements that of an LDRD team led by Elissa Chesler, which examines relationships between the bacterial residents of the cecum and the gene expression patterns in this region of the gut. Ultimately, Chesler’s team will correlate what they learn with seven genetically defined strains of mice with predispositions to specific diseases, including obesity, hypertension, and various cancers.

Since fungi represent a small fraction of the total microbiome, the JDRD team honed experimental skills in DNA extraction, to ensure that they sampled all of the organisms present in the gut material. Next, the trick was to find fungal DNA in this complex community mixture, making sure their samples were fungal specific, yet contained enough variation so all the fungi could be identified.

The team was, in fact, able to detect dozens of different fungal species in the cecum of all the mouse strains in the ORNL study; now they plan a more comprehensive study, using DNA sequencing technology at ORNL that produces over 400,000 sequencing reads in a single run.

The National Institutes of Health Human Microbiome Project is devoting over $100 million in grants over five years to this effort. This study will serve as proof of concept in competitive grant applications for one of the first studies to examine the human fungal microbiome.