VSL#3 probiotic modifies mucosal microbial composition but does not reduce colitis-associated colorectal cancer
Open accessAbstract
Although probiotics have shown success in preventing the development of experimental colitis-associated colorectal cancer (CRC), beneficial effects of interventional treatment are relatively unknown. Here we show that interventional treatment with VSL#3 probiotic alters the luminal and mucosally-adherent microbiota, but does not protect against inflammation or tumorigenesis in the azoxymethane (AOM)/Il10⁻/⁻ mouse model of colitis-associated CRC. VSL#3 (10⁹ CFU/animal/day) significantly enhanced tumor penetrance, multiplicity, histologic dysplasia scores, and adenocarcinoma invasion relative to VSL#3-untreated mice. Illumina 16S sequencing demonstrated that VSL#3 significantly decreased (16-fold) the abundance of a bacterial taxon assigned to genus Clostridium in the mucosally-adherent microbiota. Mediation analysis by linear models suggested that this taxon was a contributing factor to increased tumorigenesis in VSL#3-fed mice. We conclude that VSL#3 interventional therapy can alter microbial community composition and enhance tumorigenesis in the AOM/Il10⁻/⁻ model.
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Prior studies have shown increased tumorigenesis in murine colorectal carcinoma models treated with probiotics.
“These data are in line with previously published studies that have demonstrated increased tumorigenesis in murine models of colorectal carcinoma in probiotic-treated mice (21)”
From Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response (2021) · cites this paper as [21]
Possible probiotic mechanisms include modulation of the host microbiota, improvement of gut barrier function, and modulation of the immune system.
“The possible mechanisms of action include modulation of the host microbiota123, improvement of gut barrier function and modulation of the immune system.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [123]
Some commercially available probiotic products actually promote tumorigenesis.
“with certain formulations actually increasing tumorigenesis (144).”
From The microbiome and human cancer (2021) · cites this paper as [144]
Some studies have demonstrated an association with increased risk of bacteremia in intensive care units or tumor growth following probiotic supplementation.
“Safety needs to be primarily considered as some studies have demonstrated an association with an increased risk of bacteremia in intensive care units (Yelin et al., 2019) or tumor growth (Arthur et al., 2013) following probiotic supplementation.”
From Microbiota-centered interventions to boost immune checkpoint blockade therapies (2025) · cites this paper as Arthur et al., 2013
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References 67 · Cited by 118
Research works printed but not linked: 3
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- Authors
- Arthur, J. C., Gharaibeh, R. Z., Uronis, J. M., Perez-Chanona, E., Sha, W., Tomkovich, S., Mühlbauer, M., Fodor, A. A., & Jobin, C.
- Affiliations
- University of North Carolina at Charlotte (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Jobin, Christian
- ORCID
- Venue
- Scientific Reports
- Published
- 2013-10-08
- Volume
- 3
- Issue
- 1
- Pages
- 2868-2868
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC3792409
- OpenAlex
- W1994632618
- Cited by
- 118
- References
- 67
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 13 · 2023: 5 · 2022: 13 · 2021: 12 · 2020: 17 · 2019: 13 · 2018: 6 · 2017: 9 · 2016: 3 · 2015: 11 · 2014: 6
- FWCI
- 9.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Scientific Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- American Institute for Cancer Research
- National Institutes of Health (NIH T32, DK034987)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK47700, R01 DK73338, R01DK047700, R01DK073338, P30DK034987, T32DK007737)
- National Center for Research Resources (P40RR018603, P40 RR18603)
- Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina at Chapel Hill (P30 DK 034987)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Keywords
- colitis-associated colorectal cancer, gut microbiota, mucosal microbiota, Clostridium, tumor penetrance, carcinogenesis, inflammation
- MeSH terms
- Animals, Cell Transformation, Neoplastic, Colitis, Disease Models, Animal, Intestinal Mucosa, Colorectal Neoplasms, Mice, Knockout, Probiotics, Mice, Microbiota
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