Researchers from Brigham and Women’s Hospital, a teaching affiliate of Harvard Medical School, have developed a probiotic designed to induce multiple effects for the treatment of inflammatory bowel disease (IBD).
Multiple diseases, including IBD, are tied to the balance of gut microbes, the researchers say, suggesting restoring the right balance could help treat disease. To treat complex diseases such as IBD, a probiotic would need to serve many functions, including an ability to turn off inflammation, reverse damage and restore the gut microbiome.
Given all of these needs, researchers from Brigham and Women’s Hospital have developed what they call a “designer” probiotic, engineered to treat IBD. Preclinical results from their work are published in Nature Medicine.
“We’ve taken yeast — the very yeast that’s used to make beer — and we’ve given it the ability to sense inflammation and secrete an anti-inflammatory molecule,” said corresponding author Francisco Quintana, PhD, an investigator in the Ann Romney Center for Neurologic Diseases at the Brigham. “We call this new platform ‘Y-bots’ (yeast robots) and see the potential here for developing therapeutics that can treat diseases of the gut tissue and more.”
Previous research from the Quintana lab has explored the connection between the gut and diseases that affect the brain, suggesting potential applications for engineering probiotics beyond IBD.
Quintana and colleagues developed their probiotic using Saccharomyces cerevisiae, a species of yeast used in winemaking, baking and brewing. Using CRISPR/Cas9 gene editing technology, the researchers reportedly introduced genetic elements that could sense inflammation and respond to it by secreting an enzyme that can degrade a key molecule involved in inflammation.
The engineered yeast can secrete different levels of enzyme, depending upon how much of the inflammatory signal is present at a location in the gut. This means that the probiotic can have a highly localised response to inflammation. In mice, the engineered yeast successfully suppressed intestinal inflammation, reduced fibrosis and restored a balanced gut microbiome, the researchers say.
The team plans to complete safety studies on the probiotic while further refining and testing the engineered yeast to see if it can speed up tissue repair. Beyond IBD, the team plans to investigate the use of engineered probiotics for treating a common side effect of cancer immunotherapy, colitis.
This work was supported by the National Institutes of Health, the National MS Society, International Progressive MS Alliance and Natural Sciences Engineering Research Council of Canada.
