Researchers have modified a unique cancer-loving probiotic bacteria to release a marker that can be detected in the urine after it comes into contact with bowel cancer, even when it's in the early stages. The novel test may mean avoiding invasive procedures like colonoscopies and messy poo-based screening tests.
Globally, colorectal cancer – also known as bowel cancer – is the second leading cause of cancer-related death, with a concerning rise in incidence rates in younger populations, highlighting the importance of early detection. With bowel cancer, it’s about detecting not only cancer but its precursor, the often-benign-to-begin-with polyp.
While colonoscopy is effective at reducing the incidence of bowel cancer and its associated mortality, it’s inconvenient and costly. The commonly used poo-based tests that check for signs of cancer are certainly easier and cheaper, but they’re messy, and some people, well, would prefer not to have to do it.
Thankfully, researchers at the South Australian Health and Medical Research Institute (SAHMRI), the University of Adelaide, and Columbia University in the US have developed a less messy alternative to the poo test, using a probiotic bacteria that’s safe and already being used to treat gut disorders.
“We’ve taken advantage of this bacteria’s natural gravitation towards tumors and engineered it to release molecules that illuminate early cancers,” said Georgette Radford, one of the study’s co-authors.
The bacteria in question is a unique probiotic strain of E. coli called E. coli Nissle 1917 (EcN). It’s named after the German physician Alfred Nissle, who first isolated the strain from the gut of a German soldier during World War I after he noticed that the soldier appeared to be immune to the dysentery that was sweeping through the trenches. EcN was later proven to block and fight ‘bad’ bacteria and has enjoyed a long history of safe use in humans.
Recent research revealed another of EcN’s quirks: it’s quite fond of tumors, particularly in the gut. Rather than residing in normal tissue, it actively seeks out these tumors to live in. And it’s this quirk that the researchers in the current study exploited.
They first proved that EcN selectively and robustly colonized intestinal polyps by giving an oral dose to mouse models of bowel cancer and human colorectal cancer patients.
“Our study shows that after oral dosing, these bacteria selectively live in the gut in both the benign precursor lesions to bowel cancer, called polyps, and also bowel cancers,” Radford said.
The researchers then engineered EcN to produce a small molecule, salicylate, that could be conveniently recovered from – and detected in – bodily fluids. Orally delivering the engineered EcN to mouse models with polyps, the researchers then collected poo and urine samples. Analyzing the urine samples for the presence of salicylate 48 hours after dosing, they found the treated mice had up to five times more salicylate compared to baseline levels, whereas salicylate levels in the control animals did not change.
The researchers say the novel method could be used to non-invasively diagnose cancer early.
“Once the bacteria locates the tumor it releases a marker that we can then detect in the urine, which shows cancer is present,” said Susan Woods, a co-corresponding author. “In the future, we’re aiming to be able to detect this marker in a blood test.”
The researchers went on to see whether their engineered EcN could be used to deliver cancer therapeutics. They again engineered the bacteria, this time to release a cytokine and checkpoint inhibitor therapies at the tumor site. Following oral delivery in mouse models, the researchers observed an overall reduction of polyp area and number by about 47%, which was not limited to a specific location but was seen throughout the small intestine.
They’re confident that this platform can be used to deliver therapeutic treatment directly to the cancer site, and because EcN is ‘natural’, side effects caused by the introduction of chemotherapeutic drugs may be avoided.
The study was published in the journal Nature Communications.
Source: SAHMRI