Liver Cancer Diagnosis Now Possible with Probiotics?

Cancer continues to be the number two killer of people in the United States each year, but at least when it comes to cancers that spread to the liver, scientists may have devised a new way of diagnosing the disease using probiotics - beneficial bacteria similar to those found in yogurt.

Many types of cancer, including colon and pancreatic, tend to metastasize to the liver. And the earlier doctors can find these tumors, the more likely that they can successfully treat them.

"There are interventions, like local surgery or local ablation, that physicians can perform if the spread of disease in the liver is confined, and because the liver can regenerate, these interventions are tolerated. New data are showing that those patients may have a higher survival rate, so there's a particular need for detecting early metastasis in the liver," researcher Sangeeta Bhatia from MIT explained in a statement.

Using a harmless strain of E. coli called Nissle 1917 that colonizes the liver, engineers at both MIT and the University of California at San Diego (UCSD) programmed the bacteria to produce a luminescent signal, which can be detected with a simple urine test.

For years, scientists have been trying to successfully use bacteria as a way to combat cancer because they can survive and grow in the microenvironment where the tumor is located. This time, the MIT and UCSD researchers may have done it. Their secret is in engineering the bacterial cells to express the gene for a naturally occurring enzyme called lacZ, which cleaves lactose into glucose and galactose.

During the study, they injected a molecule containing galactose and the luminescent protein luciferin in mice. This way, when lacZ cleaves luciferin from galactose, it is easily identified in the urine.

At first, the researchers were interested in developing these bacteria for injection into patients, but then decided to investigate the possibility of delivering the bacteria orally, just like the probiotic bacteria found in yogurt.

"We realized that if we gave a probiotic, we weren't going to be able to get bacteria concentrations high enough to colonize the tumors all over the body, but we hypothesized that if we had tumors in the liver they would get the highest dose from an oral delivery," said Bhatia.

This allowed the team to develop a diagnostic specialized for liver tumors. In tests in mice with colon cancer that has spread to the liver, the probiotic bacteria colonized nearly 90 percent of the metastatic tumors.

What's more, mice given the luminescent bacteria did not exhibit any harmful side effects.

The researchers focused on the liver not only because it is a natural target for these bacteria, but also because the liver is hard to image with conventional imaging techniques like CT scanning or magnetic resonance imaging (MRI), making it difficult to diagnose metastatic tumors there.

And while these results only apply to cancers that have spread to the liver, it is certainly a positive step in the right direction for successful cancer treatments.

"These bacteria could be engineered to cause genetic disruption of cancer cell function, deliver drugs, or reactivate the immune system," added Andrea Califano from Columbia University, who was not involved in the research.

The MIT team is now pursuing the idea of using probiotic bacteria to treat cancer, as well as for diagnosing it.

The results were published in the journal Science Translational Medicine.

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