Researchers from the University of North Carolina have developed a cutting-edge approach to improve the treatment of inflammatory bowel disease (IBD) using genetically engineered probiotics.
This innovative method, detailed in their latest study published in Nature Communications, could potentially transform how medications for IBD are delivered, moving away from painful injections and infusions to a more patient-friendly oral administration.
The study was led by Juliane Nguyen, Ph.D., professor at the UNC Eshelman School of Pharmacy, and Janelle Arthur, Ph.D., associate professor at the UNC School of Medicine.
They focused on creating a more effective drug delivery system using a live biotherapeutic based on the yeast Saccharomyces boulardii, known for its safety and anti-inflammatory properties in IBD patients.
One of the significant challenges in treating IBD with probiotics is ensuring that these beneficial organisms can survive and thrive in the harsh environment of the human gut.
To address this, Nguyen and Arthur engineered Saccharomyces boulardii to express specific surface proteins that target and bind to the proteins produced by the extracellular matrix in the colon. This matrix is part of the tissue that often undergoes repair during IBD flare-ups due to ulcers.
Mairead Heavey, Ph.D., first author of the study and a former Ph.D. candidate in Nguyen’s lab, was instrumental in developing this platform.
The engineered yeast targets the upregulated proteins in the damaged extracellular matrix, allowing it to remain in the colon longer and thereby extending the probiotic’s therapeutic effects.
This targeting is crucial because it ensures that the probiotics are not only delivered directly to the areas most affected by the disease but also that they have sufficient time to exert their anti-inflammatory actions.
Over a 48-hour period, the researchers observed a hundredfold increase in probiotic concentrations in the colon of mouse models with ulcerative colitis, leading to significant improvements in inflammation and overall colon health.
Beyond simply modulating inflammation, the engineered yeast can also produce antibodies and peptides that specifically target and treat the damaged tissues in the gut.
This capability is significant because it means that the treatment can be tailored to the needs of individual patients, depending on whether they are experiencing a flare-up or are in remission.
Looking ahead, the research team plans to expand their work to explore potential treatments for other gastrointestinal conditions such as Clostridium difficile infections and colitis-associated colorectal cancer.
Although their biotherapeutic system is not yet ready for human clinical trials, the researchers are optimistic about the future. They are actively expanding their team to include clinical experts who can help bridge the gap between laboratory research and clinical application.
This breakthrough not only highlights the potential of genetically engineered probiotics in treating complex diseases like IBD but also underscores the importance of innovative approaches in medical research that can lead to more effective and less invasive treatments for patients.
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The research findings can be found in Nature Communications.
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