Bifidobacterium inhibits the progression of colorectal tumorigenesis in mice through fatty acid isomerization and gut microbiota modulation
Open accessAbstract
Colorectal cancer (CRC) represents the third most common cancer worldwide. Consequently, there is an urgent need to identify novel preventive and therapeutic strategies for CRC. This study aimed to screen for beneficial bacteria that have a preventive effect on CRC and to elucidate the potential mechanisms. Initially, we compared gut bacteria and bacterial metabolites of healthy volunteers and CRC patients, which demonstrated that intestinal conjugated linoleic acid (CLA), butyric acid, and Bifidobacterium in CRC patients were significantly lower than those in healthy volunteers, and these indicators were significantly negatively correlated with CRC. Next, spontaneous CRC mouse model were conducted to explore the effect of supplemental CLA-producing Bifidobacterium on CRC. Supplementation of mice with CLA-producing Bifidobacterium breve CCFM683 and B. pseudocatenulatum MY40C significantly prevented CRC. Moreover, molecular approaches demonstrated that CLA and the CLA-producing gene, bbi, were the key metabolites and genes for CCFM683 to prevent CRC. Inhibitor intervention results showed that PPAR-γ was the key receptor for preventing CRC. CCFM683 inhibited the NF-κB signaling pathway, up-regulated MUC2, Claudin-1, and ZO-1, and promoted tumor cell apoptosis via the CLA-PPAR-γ axis. Additionally, fecal microbiota transplantation (FMT) and metagenomic analysis showed that CCFM683 up-regulated Odoribacter splanchnicus through CLA production, which then prevented CRC by producing butyric acid, up-regulating TJ proteins, regulating cytokines, and regulating gut microbiota. These results will contribute to the clinical trials of Bifidobacterium and the theoretical research and development of CRC dietary products.
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The Odoribacter genus is strongly associated with bile acids and short-chain fatty acids.
“This certain bacterial genus was strongly associated with the bile acids (BAs) and short-chain fatty acids (SCFAs) (Chen et al. 2025; Sato et al. 2021).”
From Odoribacter laneus protects intestinal barrier by bile acid-FXR axis in acute pancreatitis (2026) · cites this paper as Chen et al. 2025
The Results section (Effects of O. splanchnicus on CRC mice; page unavailable) reports that O. splanchnicus treatment significantly increased butyric acid, a short-chain fatty acid, but did not increase the other short-chain fatty acids measured. Our copy does not report an association between Odoribacter and bile acids, so it does not support the full claim. (LLM, conf=0.87)
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- Authors
- Chen, Y., Fang, H., Chen, H., Liu, X., Zhao, J., Stanton, C., Ross, R. P., Chen, W., & Yang, B.
- Affiliations
- Jiangnan University (CN)
- Corresponding author
- Yang, Bo
- Venue
- Gut Microbes
- Publisher
- Informa UK Limited
- Published
- 2025-02-09
- Volume
- 17
- Issue
- 1
- Pages
- 2464945-2464945
- ISSN
- 1949-0976 (ISSN-L)
- 1949-0984
- PMC
- PMC11812354
- OpenAlex
- W4407344149
- Cited by
- 44
- References
- 64
- Citations by year
- 2026: 23 · 2025: 21
- FWCI
- 13.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Gut Microbes (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion, cc-by)
- Funders
- National Natural Science Foundation of China
- Fundamental Research Funds for the Central Universities
- Collaborative Innovation Center of Food Safety and Quality Control
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
- Keywords
- Bifidobacterium, colorectal cancer, colorectal carcinogenesis, conjugated linoleic acid, fatty acid isomerization, gut microbiota, PPARγ, NF-κB signaling, butyrate, Odoribacter splanchnicus, tight junction proteins, tumor cell apoptosis, fecal microbiota transplantation
- MeSH terms
- Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Animals, Bacteria, Bifidobacterium, Disease Models, Animal, Fatty Acids, Female, Humans, Male, Mice, Inbred C57BL, Middle Aged, Colorectal Neoplasms, NF-kappa B, Apoptosis, Disease Progression, Probiotics, Butyric Acid, Linoleic Acids, Conjugated, PPAR gamma, Mice, Carcinogenesis
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