Understanding the molecular foundations of intestinal host-microbial relationships is an exceedingly challenging problem due to the complexity of the gut microbiota, the complexity of the intestinal mucosal surface, and the lack of good in vitro models for studying the complex interplay between host and microbe. Overcoming these challenges has required the development of unique in vivo experimental approaches. One of our most important tools is gnotobiotics ("known life"), a technology involving the use of microbiologically sterile ("germ-free") animals. Using germ-free mice, we can manipulate the intestinal ecosystem by introducing a single bacterial species or defined species mixtures. We can then combine gnotobiotics with a battery of tools for molecular analysis in order to study bacterial-epithelial crosstalk in the gut.

The Hooper lab maintains a gnotobiotic mouse facility here at UT Southwestern, where we rear mice under germ-free conditions in sterile plastic isolators (below, left). Food and water and other sterile supplies are imported into the isolators by docking autoclaved supply cylinders to a double-door port built into the isolator wall (below, right). We monitor our germ-free mice monthly for the presence of microbial contamination to ensure the sterility of the colony.