Engineered spermidine-secreting <i>Saccharomyces boulardii</i> ameliorate colitis and colon cancer in mice
Why this work is in the frame
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Bibliographic record
Abstract
Abstract 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 transposon-mediated gene integration to manipulate expression of key enzymes in the polyamine synthetic and transport pathways. We tested the engineered yeast by oral gavage of mice treated with azoxymethane and dextran sulfate sodium to induce chronic colitis and colon 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 dextran sulfate sodium-induced colitis as well as colitis-associated colon cancer 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 colon cancer.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it