Yeast in Gut Shows Promise for Targeted Drug Delivery: New Study
A new study is offering a deeper understanding of how yeast cells behave within the gut, potentially paving the way for more effective, targeted drug delivery systems. Researchers are optimistic that this knowledge will lead to the development of new yeast strains capable of producing therapeutic drugs with greater efficiency, tailored to specific diseases.
“Yeast is promising as a drug-delivery platform,” explains Nathan Crook, associate professor of chemical and biomolecular engineering at North Carolina State University and the study’s corresponding author. While previous research has demonstrated yeast’s ability to be modified to produce therapeutic molecules – including those that reduce inflammation and combat disease – the precise mechanisms behind this process remained largely unknown. “We knew yeasts could do this, but we didn’t know how,” Crook says. “Which genes are turned off or on? What is the yeast eating? Is the yeast producing any other molecules that might be harmful?”
The research team focused on Saccharomyces boulardii (Sb) yeast, a species already utilized as a probiotic. Despite its existing use, the biochemical processes within Sb have been relatively understudied. To address this gap, the researchers utilized a readily available, unmodified strain of Sb yeast and introduced it into laboratory mice specifically bred to be “germ-free” – meaning they lack a natural gut microbiome. This controlled environment allowed for a clearer analysis of the yeast’s activity.
By collecting fecal and intestinal samples from these mice, the researchers employed a combination of established and novel analytical techniques to measure RNA production within the yeast cells as they traversed the digestive system. The germ-free environment was crucial, eliminating interference from other microbial RNA and allowing for precise identification of yeast-derived genetic material.
“One of the key findings is that we’ve identified which genes in the Sb yeast are much more likely to be activated when in the gut as opposed to other environments,” Crook explains. “That tells us which sections of DNA are most responsive to the gut environment. And that is useful because People can then target these ‘promoter’ sections of DNA as on-switches that tell the yeast cell when to start producing therapeutic molecules. In other words, we’ve identified the best candidates for helping us ensure the yeast cell is producing medicine when we want it to, which makes it a much more efficient drug-delivery platform.”
Importantly, the study also revealed that genes associated with potentially harmful behaviors in the yeast were not activated within the gut environment. This finding is reassuring, given the established safety profile of Sb as a probiotic. “This isn’t surprising, given that Sb yeast is already used as a probiotic – which would be unlikely if it was causing intestinal problems. However, it’s good to establish this before moving forward with additional efforts to engineer Sb cells for drug delivery,” Crook noted.
Further analysis indicated that the gut environment isn’t particularly nutrient-rich for the yeast. The researchers observed that the yeast cells were primarily metabolizing lipids (fats) rather than carbohydrates. “This is not entirely surprising, but it’s important because if we want the yeast cells to essentially serve as factories that produce medicine on-site, then you need those cells to have energy to do their work efficiently,” Crook says. “Our findings suggest it may be beneficial to modify the yeast cells so that they can make better use of the complex carbohydrates in the gut ecosystem.”
This research builds upon previous work exploring yeast as a therapeutic delivery system. In , researchers at the University of North Carolina Chapel Hill published a study demonstrating the successful engineering of Saccharomyces boulardii to deliver drugs and reduce inflammation in mouse models of inflammatory bowel disease (IBD). That study, led by Juliane Nguyen, PhD, and Janelle Arthur, PhD, showed that their engineered probiotic strain boosted probiotic concentrations and prolonged yeast survival in the gut, ultimately inhibiting and even reversing inflammation. The UNC team’s work focused on creating a “live biotherapeutic” that could secrete specific medications, potentially eliminating the need for injections or infusions for IBD patients.
Similarly, research published in highlighted the potential of using a yeast probiotic to deliver immunotherapy directly to tumors within the gastrointestinal tract, shrinking tumors in mice. This approach offers a potentially novel strategy for cancer treatment.
The current study, published in the journal BMC Genomics, provides a crucial foundation for these ongoing efforts. The researchers have filed patent applications and invention disclosures related to the engineering of probiotic yeast. The work was supported by funding from the National Science Foundation, the Novo Nordisk Foundation, and the National Institutes of Health.
“We’re optimistic about the potential of Saccharomyces boulardii for the development of new pharmaceuticals, and this work provides a roadmap for the most promising paths forward,” Crook concludes.