Deconjugating taurocholic acid with Bifidobacterium to mitigate obesity-driven cancer progression by restoring CD8+ T-cell infiltration
Abstract Obesity is linked to an increased cancer risk, and probiotics show promise in weight management. Here, we elucidate the precise mechanisms through which the probiotic Bifidobacterium breve (B. breve) modulates the immune response in obesity-associated tumours utilizing a Hepa1-6 cell-bearin...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | npj Biofilms and Microbiomes |
| Online Access: | https://doi.org/10.1038/s41522-025-00809-4 |
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| author | Ruoshui Yuan Yuke Li Yifei Wang Qingxiang Li Chuanbin Guo Lin Wang |
| author_facet | Ruoshui Yuan Yuke Li Yifei Wang Qingxiang Li Chuanbin Guo Lin Wang |
| author_sort | Ruoshui Yuan |
| collection | DOAJ |
| description | Abstract Obesity is linked to an increased cancer risk, and probiotics show promise in weight management. Here, we elucidate the precise mechanisms through which the probiotic Bifidobacterium breve (B. breve) modulates the immune response in obesity-associated tumours utilizing a Hepa1-6 cell-bearing hepatocellular carcinoma (HCC) model sensitive to high-fat diet (HFD)-induced obesity. HFD-induced obesity expedited HCC progression and fostered an immunosuppressive microenvironment. Treatment with B. breve enhanced cancer control by rescuing the local infiltration of antitumour immune cells. Elevated serum taurocholic acid (TCA) levels were negatively correlated with B. breve levels in obese HCC mice. TCA hindered the infiltration of CD8+ T cells into the tumour microenvironment and diminished their antitumour efficacy by blocking ERK phosphorylation. B. breve deconjugated TCA via its type 4 bile salt hydrolase (BSH), and this effect was diminished upon BSH inhibition by AAA-10. These results highlight the potential application of the probiotic B. breve in the multidisciplinary treatment of cancer in obese individuals. |
| format | Article |
| id | doaj-art-65cf74b0f39147b29180fd210989ca41 |
| institution | Kabale University |
| issn | 2055-5008 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Biofilms and Microbiomes |
| spelling | doaj-art-65cf74b0f39147b29180fd210989ca412025-08-24T11:10:43ZengNature Portfolionpj Biofilms and Microbiomes2055-50082025-08-0111111910.1038/s41522-025-00809-4Deconjugating taurocholic acid with Bifidobacterium to mitigate obesity-driven cancer progression by restoring CD8+ T-cell infiltrationRuoshui Yuan0Yuke Li1Yifei Wang2Qingxiang Li3Chuanbin Guo4Lin Wang5Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of StomatologyStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Zhejiang Key Laboratory of Oral BiomedicalDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of StomatologyDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of StomatologyDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of StomatologyDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of StomatologyAbstract Obesity is linked to an increased cancer risk, and probiotics show promise in weight management. Here, we elucidate the precise mechanisms through which the probiotic Bifidobacterium breve (B. breve) modulates the immune response in obesity-associated tumours utilizing a Hepa1-6 cell-bearing hepatocellular carcinoma (HCC) model sensitive to high-fat diet (HFD)-induced obesity. HFD-induced obesity expedited HCC progression and fostered an immunosuppressive microenvironment. Treatment with B. breve enhanced cancer control by rescuing the local infiltration of antitumour immune cells. Elevated serum taurocholic acid (TCA) levels were negatively correlated with B. breve levels in obese HCC mice. TCA hindered the infiltration of CD8+ T cells into the tumour microenvironment and diminished their antitumour efficacy by blocking ERK phosphorylation. B. breve deconjugated TCA via its type 4 bile salt hydrolase (BSH), and this effect was diminished upon BSH inhibition by AAA-10. These results highlight the potential application of the probiotic B. breve in the multidisciplinary treatment of cancer in obese individuals.https://doi.org/10.1038/s41522-025-00809-4 |
| spellingShingle | Ruoshui Yuan Yuke Li Yifei Wang Qingxiang Li Chuanbin Guo Lin Wang Deconjugating taurocholic acid with Bifidobacterium to mitigate obesity-driven cancer progression by restoring CD8+ T-cell infiltration npj Biofilms and Microbiomes |
| title | Deconjugating taurocholic acid with Bifidobacterium to mitigate obesity-driven cancer progression by restoring CD8+ T-cell infiltration |
| title_full | Deconjugating taurocholic acid with Bifidobacterium to mitigate obesity-driven cancer progression by restoring CD8+ T-cell infiltration |
| title_fullStr | Deconjugating taurocholic acid with Bifidobacterium to mitigate obesity-driven cancer progression by restoring CD8+ T-cell infiltration |
| title_full_unstemmed | Deconjugating taurocholic acid with Bifidobacterium to mitigate obesity-driven cancer progression by restoring CD8+ T-cell infiltration |
| title_short | Deconjugating taurocholic acid with Bifidobacterium to mitigate obesity-driven cancer progression by restoring CD8+ T-cell infiltration |
| title_sort | deconjugating taurocholic acid with bifidobacterium to mitigate obesity driven cancer progression by restoring cd8 t cell infiltration |
| url | https://doi.org/10.1038/s41522-025-00809-4 |
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