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Engineered Probiotic Saccharomyces boulardii Reduces Colitis-Associated Colorectal Cancer Burden in Mice
Tyler Culpepper1, Krithika Senthil2, Jessica Vlcek3
1Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Digestive Diseases and Sciences
|March 29, 2025
Summary
Engineered probiotic bacteria reduced colorectal cancer tumors in mice with inflammatory bowel disease. Further optimization is needed to improve colonization and anti-cancer efficacy.
Area of Science:
- Gastroenterology
- Microbiology
- Oncology
Background:
- Inflammatory bowel diseases (IBD) increase colorectal cancer (CRC) risk due to chronic inflammation.
- Current systemic immunosuppressants have severe side effects.
- Live oral biotherapeutics offer targeted intestinal treatment.
Purpose of the Study:
- To evaluate the anti-cancer potential of engineered Saccharomyces boulardii in a mouse model of IBD-associated CRC.
- To assess the efficacy of engineered S. boulardii in reducing inflammation and tumorigenesis.
Main Methods:
- Azoxymethane-treated interleukin 10-deficient (AOM/Il10-/-) mice were used to model IBD-associated CRC.
- Mice received engineered S. boulardii, unmodified S. boulardii, or placebo orally for 18 weeks.
- Colons were analyzed for inflammation and tumor development.
Main Results:
- Both engineered and unmodified S. boulardii reduced histological colon inflammation with twice-weekly dosing.
- Engineered S. boulardii demonstrated a dose-dependent reduction in gross tumor number (median 7.5 to 2 per mouse).
- Engineered S. boulardii did not show enhanced colonization compared to the unmodified strain.
Conclusions:
- Engineering S. boulardii did not improve its ability to reduce inflammation-associated tumorigenesis.
- Further optimization of host-binding targets is necessary to enhance colonization and anti-cancer effects of engineered probiotics.
Keywords:
Colitis-associated cancerColorectal cancerInflammatory bowel diseasesLive biotherapeuticProbioticSaccharomyces boulardii
