Scientific reportsAug 30, 2025

Modified yeast that releases spermidine reduces colon inflammation and cancer in mice

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jan 20, 2026

Abstract

Spermidine-secreting S. boulardii strains were significantly more effective than wild-type S. boulardii in reducing colitis symptoms.

The engineered S. boulardii was designed to produce and release spermidine, a natural compound that supports tissue regeneration.
Oral administration of spermidine-secreting S. boulardii populated the gastrointestinal tract with active cells and increased free spermidine levels.
In mouse models, the modified yeast reduced symptoms of colitis and decreased the risk of colitis-associated cancer.
These findings may indicate a potential therapeutic approach for treating inflammatory bowel disease and its complications.

Simplified

Experimental studies suggest that the probiotic yeast Saccharomyces boulardii can mitigate the symptoms of inflammatory bowel disease. However, these results are equivocal and S. boulardii probiotic therapy has not gained widespread acceptance in clinical practice. To assess whether the therapeutic properties of S. boulardii might be improved upon, we engineered S. boulardii to overproduce and secrete spermidine, a pro-regenerative natural metabolite. We employed CRISPR gene deletion and integration of gene cassettes at the Ty2 locus to achieve high level polyamine synthesis and transport. We tested whether spermidine secreting S. boulardii could reduce disease symptoms in dextran sulfate sodium (DSS) and azoxymethane induced models of intestinal inflammation and cancer. We demonstrate that oral delivery of spermidine-secreting S. boulardii in mice populates the gastrointestinal tract with viable spermidine-secreting S. boulardii cells and raises free spermidine levels in the gastrointestinal tract. Strikingly, spermidine-secreting S. boulardii strains were significantly more effective than wild-type S. boulardii in reducing colitis symptoms as well as colitis-associated carcinogenesis in mice. These results suggest that in situ spermidine secretion by engineered synthetic biotic yeast strains may be an effective and low-cost therapy to mitigate inflammatory bowel disease and associated colon cancer.