Yogurt laced with bacteria may serve as a test for cancer in the liver

Tal Danino rewired the genetic circuitry of Escherichia coli to detect cancer in urine.
Photo: Chris Bickel/Science Translational Medicine
Tal Danino rewired the genetic circuitry of Escherichia coli to detect cancer in urine. Photo: Chris Bickel/Science Translational Medicine

Eating a spoonful of probiotic-fortified yogurt, followed by a quick urine test, may someday be enough to tell if cancer has spread to your liver.

In a study published in this week’s issue of Science Translational Medicine, researchers present a rapid, non-invasive way to detect liver cancer that’s shown promise in tests in mice. Their approach: hijack the body’s digestive system and use bacteria as messengers.

Cancers commonly recur in the liver long after the cells have disappeared from other organs. Researchers are still exploring reasons why that’s the case, but they do know that because the liver can regrow, patients have a high chance of recovery — if the cancer’s caught quickly.

“New data are showing that those patients have a higher survival rate, so there’s a particular need for detecting early metastasis in the liver,” said Sangeeta Bhatia, director of the Laboratory for Multiscale Regenerative Technologies at MIT, who worked on the study.

The catch is that because liver tumors tend to be small and dispersed, they can be hard to detect using imaging techniques. A better way, Bhatia and team propose in their new study, is to use bacteria as tumor scouts — the microbes have long been known to thrive in these nutrient-rich zones — and engineer them to emit a signal once they reached the mass and multiply. That indicator then can be detected in the person’s urine.

This is where the probiotic yogurt comes in: It turns out the best way to get the bacteria into the liver is to eat them mixed into a parfait, say, and let the bugs make their way through the digestive system.

In their study, the researchers picked a harmless strain of E. coli called Nissle 1917, which is marketed as a promoter of gastrointestinal health.

“This is a safe and widely used probiotic,” said Arthur Prindle, currently a post-doctoral student at UCSD, who along with MIT postdoc Tal Danino, is a lead author on the paper. “In fact, we were able to order it from Amazon and engineer it to express the genes we wanted.”

The researchers fed the bacteria-laced yogurt to the rodents. When the bacteria reached the liver, it was designed to release enzymes if it encountered a tumor. The rodents were then injected with a compound that interacted with the enzymes, releasing a molecule that was excreted in urine.

This paper demonstrates the potential of engineered probiotic bacteria with synthetic circuits to enable diagnostics in the body, says Timothy Lu of the Research Laboratory of Electronics at MIT, a core member of the institute’s Synthetic Biology Center. “The ability to sense disease states and trigger outputs that can show up in the urine opens up new possibilities for non-invasive disease monitoring with useful applications for clinical medicine.”

Extensive testing is needed before it reaches a clinic, but Bhatia is an experienced hand at commercializing lab discoveries. She won the $500,000 Lemelson-MIT Prize in 2014, previously worked on a method to detect colorectal cancer using nanoparticles, and is also the co-founder of two biotech companies Hepregen and Zymera.

Bhatia said the group has already filed patents to allow commercial investment in this new technology. Currently, the MIT team is working on understanding the trafficking of probiotics from the gut to the liver and exploring therapeutic as well as diagnostic strains.