Researchers at North Carolina State University, including Nathan Crook, investigated how the probiotic yeast Saccharomyces boulardii (Sb) behaves inside the gut to support new approaches for delivering therapeutic molecules. They selected Sb because it is the only yeast species currently used as a probiotic, yet its biochemical behaviour in the gut was not well characterized.
In a controlled experiment the team introduced an off-the-shelf, non‑genetically modified Sb strain into germ-free mice and collected fecal and intestinal samples. Using a novel combination of established sampling and analytical techniques, they measured the RNA the yeast produced while passing through the animals. Because the mice had no other microbes, the researchers could identify yeast RNA more clearly than in a normal microbiome.
Key findings included identification of genes and promoter regions that are preferentially activated in the gut. These promoter sections can act as on-switches, so targeting them could allow engineered yeast to begin producing therapeutics at the right time and place, improving drug delivery efficiency. The study also found that genes associated with potentially pathogenic behaviour were not activated in the gut, reinforcing Sb's safety profile and supporting further engineering efforts.
Gene activity patterns indicated the gut is not particularly nutrient-rich for Sb: the yeast appeared to digest more lipids than carbohydrates. The authors suggest modifying Sb to better utilise complex carbohydrates in the gut to fuel therapeutic production. The results are published in BMC Genomics. The authors have filed patent applications and invention disclosures, and the work was supported by the National Science Foundation, the Novo Nordisk Foundation, and the National Institutes of Health.
Difficult words
- probiotic — live microorganisms used to improve health
- germ-free — free of other microbes or germs
- microbiome — community of microorganisms in an environment
- promoter — section that can act as an on-switch
- pathogenic — likely to cause disease or harm
- lipid — a fat or fat-like biological moleculelipids
- carbohydrate — a sugar or starch molecule used for energycarbohydrates
Tip: hover, focus or tap highlighted words in the article to see quick definitions while you read or listen.
Discussion questions
- How could targeting gut-activated promoter sections improve the timing and location of therapeutic delivery? Give reasons.
- Given that potentially pathogenic genes were not activated, what safety concerns should researchers still consider when engineering Sb?
- What benefits and challenges might arise from modifying Sb to better utilise complex carbohydrates in the gut?
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