Bifidobacterium inhibits the progression of colorectal tumorigenesis in mice through fatty acid isomerization and gut microbiota modulation

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 mec...

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Main Authors: Yang Chen, Huiting Fang, Haiqin Chen, Xiaoming Liu, Jianxin Zhao, Catherine Stanton, R. Paul Ross, Wei Chen, Bo Yang
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Gut Microbes
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Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2025.2464945
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author Yang Chen
Huiting Fang
Haiqin Chen
Xiaoming Liu
Jianxin Zhao
Catherine Stanton
R. Paul Ross
Wei Chen
Bo Yang
author_facet Yang Chen
Huiting Fang
Haiqin Chen
Xiaoming Liu
Jianxin Zhao
Catherine Stanton
R. Paul Ross
Wei Chen
Bo Yang
author_sort Yang Chen
collection DOAJ
description 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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spelling doaj-art-2fc15f845f45442da97808ba26f3a5842025-08-20T03:22:19ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2464945Bifidobacterium inhibits the progression of colorectal tumorigenesis in mice through fatty acid isomerization and gut microbiota modulationYang Chen0Huiting Fang1Haiqin Chen2Xiaoming Liu3Jianxin Zhao4Catherine Stanton5R. Paul Ross6Wei Chen7Bo Yang8State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, ChinaState Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, ChinaState Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, ChinaState Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, ChinaState Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, ChinaInternational Joint Research Laboratory for Maternal-Infant Microbiota and Health, Jiangnan University, Wuxi, Jiangsu, ChinaInternational Joint Research Laboratory for Maternal-Infant Microbiota and Health, Jiangnan University, Wuxi, Jiangsu, ChinaState Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, ChinaState Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, ChinaColorectal 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.https://www.tandfonline.com/doi/10.1080/19490976.2025.2464945Bifidobacteriumcolorectal cancerconjugated linoleic acidPPAR-γOdoribacter splanchnicusbutyric acid
spellingShingle Yang Chen
Huiting Fang
Haiqin Chen
Xiaoming Liu
Jianxin Zhao
Catherine Stanton
R. Paul Ross
Wei Chen
Bo Yang
Bifidobacterium inhibits the progression of colorectal tumorigenesis in mice through fatty acid isomerization and gut microbiota modulation
Gut Microbes
Bifidobacterium
colorectal cancer
conjugated linoleic acid
PPAR-γ
Odoribacter splanchnicus
butyric acid
title Bifidobacterium inhibits the progression of colorectal tumorigenesis in mice through fatty acid isomerization and gut microbiota modulation
title_full Bifidobacterium inhibits the progression of colorectal tumorigenesis in mice through fatty acid isomerization and gut microbiota modulation
title_fullStr Bifidobacterium inhibits the progression of colorectal tumorigenesis in mice through fatty acid isomerization and gut microbiota modulation
title_full_unstemmed Bifidobacterium inhibits the progression of colorectal tumorigenesis in mice through fatty acid isomerization and gut microbiota modulation
title_short Bifidobacterium inhibits the progression of colorectal tumorigenesis in mice through fatty acid isomerization and gut microbiota modulation
title_sort bifidobacterium inhibits the progression of colorectal tumorigenesis in mice through fatty acid isomerization and gut microbiota modulation
topic Bifidobacterium
colorectal cancer
conjugated linoleic acid
PPAR-γ
Odoribacter splanchnicus
butyric acid
url https://www.tandfonline.com/doi/10.1080/19490976.2025.2464945
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