These shiny bacteria can diagnose intestinal problems

Researchers at Rice University and the University of Colorado School of Medicine have designed and tested E.coli bacteria capable of detecting signs of inflammatory bowel disease (IBD) in mice.

They believe it’s more than a new way to diagnose gut problems — it’s also a big step forward for synthetic biology, taking artificial life from the lab to the clinic.

What is IBD? Episodes of inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease, are often accompanied by high acidity in the intestines, a condition called acidosis.

“Normally the pH in your intestines is around seven, which is neutral, but you get a lot of inflammation in Crohn’s disease, and the pH goes to something like three, which is very acidic,” Jeffrey Tabor, associate professor of bioengineering and biosciences at Rice and co-author of the study, said in a declaration.

It is to this acidic environment that glowing bacteria react, changing their glowing colors to warn of an IBD outbreak. It is a new practical application for synthetic biology.

What is synthetic biology? Simply put, synthetic biology is the science of redesigning living organisms for specific tasks. Organisms can be modified to clean up pollutants (a process known as bioremediation) Where create rubber and fuelamong a myriad of other potential uses.

Using synthetic biology to create bacterial sensors for disease takes advantage of millions of years of evolution, Rice says. During this period, bacteria have developed a set of “specific and sensitive” genetic circuits that they use to sense their environment; synthetic biology uses these sensors for our own purposes.

For example, researchers at MIT have developed a “bacteria-on-a-chip” test that uses E.coli to detect gastric ulcers, which would usually require an endoscope to diagnose definitively – and sedation.

“The goal of this sensor is that you could bypass an unnecessary procedure by simply ingesting the capsule, and within a relatively short time you would know whether or not there was a bleeding event,” MIT lead author Mark Mimee said.

Bacterial diagnosis: Tabor’s group has already designed E.coli change color to diagnose digestive diseases.

“The gut is home to billions of microorganisms that play key roles in health and disease,” Tabor said. New Atlas in 2017. “However, it is a dark and relatively inaccessible place, and little technology has been developed to study these processes in detail.”

His current collaborator, Colorado immunology professor Sean Colgan, pointed outspecifically, “It turns out that measuring pH in the gut by non-invasive means is quite difficult.”

But those tens of thousands of genetic sensors in bacteria can do the job very well.

Rice’s Ph.D. student Kathryn Brink had discovered pH-sensing circuits in 2019, while demonstrating a synthetic biology plug-and-play toolkit. Colgan read about the sensor and wondered if the bacteria could be used to detect Crohn’s disease in a mouse model.

Brink prepared part of the acidosis reaction E.coliarming them with a gene that causes bacteria to glow different colors in acidic environments, ranging from red to green.

Colgan’s lab is studying genes that are turned on and off during acidosis and wanted to use the bacteria to see if what they saw in the lab would also happen in animals.

When presented to a mouse model for Crohn’s disease, the E.coli did exactly what synthetic biology designed them to do, their glow changing from red to green.

“Colonization of this bacterial strain was the perfect biological tool to monitor acidosis during active inflammation,” Colgan said. The bacterium serves as a “useful and valuable set of biomarkers” to tell if there was active intestinal inflammation.

A colorful bowl: While the technique, published in PNAShasn’t yet been tested in humans, the mouse genes that turn on and off during acidosis that Colgan studies have also been observed in humans with Crohn’s flares.

Tabor expects human clinical trials to begin within the next few years and imagines a near future where synthetic biology produces a colorful bowl that could reveal real-time information about your intestines.

“We think it could be added to food and programmed to turn toilet water blue to warn patients when a flare-up is just beginning,” he said.

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