Bacterial reporters that get the scoop (Silver)

It's a jungle in there. In the tightly woven ecosystem of the human gut, trillions of bacteria compete with each other on a daily basis while they sense and react to signals from the immune system, ingested food, and other bacteria.

Problems arise when bad gut bugs overtake friendly ones, or when the immune system is thrown off balance, as in Crohn's disease, celiac disease, and colorectal cancer. Doctors have struggled to diagnose these conditions early and accurately. But now a new engineered strain of E. coli bacteria could deliver status updates from this complex landscape to help keep gastrointestinal diseases at bay.

The new strain non-destructively detected and recorded an environmental signal in the mouse gut, and remembered what it "saw." The advance, reported in the Proceedings of the National Academy of Sciences, could lead to a radically new screening tool for human gut health.

The key to turning E. coli into gut reporters was to insert a well-known genetic switch that flips when it senses a specific environmental cue. This switch confers on the cells the ability to "remember" what they sense for up to a week — long enough for scientists to recover fecal samples and test whether the switch has flipped.

"This achievement paves the way toward living monitors programmed using synthetic gene circuits," said Wyss Institute Core Faculty member Pamela Silver, Ph.D., senior author on the study who is also the Elliott T. and Onie H. Adams Professor of Biochemistry and Systems Biology at Harvard Medical School (HMS). Silver's team included James Collins, Ph.D., who is also a Wyss Core Faculty member and professor of bioengineering at Boston University, as well as other collaborators from the Wyss Institute, Harvard Medical School and Boston University. "It could lead to new diagnostics for all sorts of complex environments."

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