Humans have an uneasy relationship with bacteria – sure, they can make us very sick, but we also couldn't live without the complex society residing in our guts. Now, researchers at Rice University have engineered E. coli to help detect inflammation in the colon of mice by infiltrating that microbiome and sending color signals through their feces. Eventually this could lead to self-diagnosis tests for humans ... and if your poop turns out blue, you should probably see a doctor.
With so many different organisms calling the human gut home, it can be hard to study exactly what's causing a particular health problem. In some cases, the tools don't exist to reliably diagnose conditions, so bacteria engineered to react to certain biomarkers could help fill that role.
"The gut harbors trillions of microorganisms that play key roles in health and disease," says Jeffrey Tabor, lead author of the study. "However, it is a dark and relatively inaccessible place, and few technologies have been developed to study these processes in detail. On the other hand, bacteria have evolved tens of thousands of genetically encoded sensors, many of which sense gut-linked molecules. Thus, genetically engineered sensor bacteria have tremendous potential for studying gut pathways and diagnosing gut diseases."
For the study, the Rice team focused on detecting colitis, a condition where the colon becomes inflamed. Previous studies had shown evidence that elevated levels of a molecule known as thiosulfate might be a biomarker for the condition, so the researchers engineered E. coli that could sense thiosulfate and respond by producing proteins that fluoresced green.
To test the system, the team gave billions of the bacteria to two groups of mice: a healthy control group and a group suffering from colitis. As expected, the feces of the mice with colitis glowed green when viewed under an instrument called a flow cytometer, indicating elevated levels of thiosulfate and, by extension, the presence of colitis. The more inflamed the mouse's colon was, the brighter their poop glowed.
As usual with mouse studies, there's no guarantee that thiosulfate is a biomarker for colitis in humans, but with a bit more research, the general principle of using engineered bacteria to sense and fluoresce as a diagnosis tool could carry across. Eventually, the researchers say, a system could be developed where the bacteria express a colored pigment that can be spotted without the use of lab equipment, to allow amateur diagnoses of certain conditions at home.
"We'd like to develop a home inflammation test where a person prone to colitis flare-ups would eat yogurt that contained the engineered bacteria and see blue pigment in the toilet if they were sick," says Tabor.
The research was published in the journal Molecular Systems Biology.
Source: Rice University