Melius MicroBiomics Inc., a biotechnology company spun out of UBC Okanagan, is preparing to take its engineered microbial therapeutic to human trials in Australia this summer.
A probiotic bioengineered by UBC Okanagan researchers to thrive in the inflamed gut is set to enter human clinical trials, capping a decade-long effort to turn a beneficial bacterium into a treatment for inflammatory bowel disease.
The strategy, detailed in a proof-of-concept study published in Gastroenterology , tackles a stubborn problem in microbiome medicine: getting beneficial bacteria to survive in a gut that's actively inflamed.
An inflamed gut is why probiotics have largely failed to produce clinical effects, as UBCO's Drs. Deanna Gibson and Andrea Verdugo-Meza have previously demonstrated .
Trials are scheduled to begin in Australia this August.
"We worked for over a decade to get to this point," says Dr. Gibson, a professor of biology in the Irving K. Barber Faculty of Science and the study's senior author. "Probiotics tend to wash out of the gut exactly when patients need them most-during a flare. We wanted to flip that and engineer the probiotic to use inflammation as fuel."
The research focuses on Escherichia coli Nissle 1917, a probiotic that has been safely used in humans to treat intestinal conditions for more than a century.
On its own, it may help keep ulcerative colitis in remission but does little once active disease sets in. The UBCO team added a set of genes that lets the bacterium use a compound produced during inflammation as fuel, giving it a competitive advantage precisely when the gut is inflamed.
The study was carried out by Dr. Verdugo-Meza, who completed her PhD in Gibson's lab, and Sandeep Gill, a former MSc student in Dr. Gibson's lab.
Dr. Verdugo-Meza led the work to understand and validate how the technology functions, conducting immune cell and live animal studies at the heart of the research.
"What's encouraging is the breadth of the effect," says Dr. Verdugo-Meza. "We saw improvements in the gut barrier, the immune response and the microbial community-not just one pathway. And it worked with low, infrequent dosing and without antibiotics."
The modified strain bloomed during active colitis in mice, then receded as the animals recovered. It outperformed both the unmodified probiotic and standard first-line drugs for mild to moderate ulcerative colitis.
In one chronic model, untreated mice and those given the standard probiotic developed severe colitis, while no mice in the engineered-probiotic group did by the 16-week mark.
The strain is patented by UBC and licensed to Melius MicroBiomics, a UBC Okanagan spin-off company co-founded by Dr. Gibson.
The UBCO live biotherapeutic appears to strengthen the gut's protective barrier, shift the immune environment toward a calmer state and nudge the resident microbiome toward more beneficial bacteria.
The pending human trials come after testing in several mouse models and lab-grown human colon tissue. The researchers have also completed a successful porcine trial to support human regulatory approvals.
The researchers indicate the approach could open a broader path for microbiome medicine.
"If we can design microbes to colonize exactly where and when they're needed," says Dr. Gibson, "we open up a whole category of treatments that work with the body's biology rather than against it."
