The microbiota-derived bile acid taurodeoxycholic acid improves hepatic cholesterol levels in mice with cancer cachexia
Alterations in bile acid profile and pathways contribute to hepatic inflammation in cancer cachexia, a syndrome worsening the prognosis of cancer patients. As the gut microbiota impinges on host metabolism through bile acids, the current study aimed to explore the functional contribution of gut micr...
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| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2025.2449586 |
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| author | Morgane M. Thibaut Martin Roumain Edwige Piron Justine Gillard Axelle Loriot Audrey M. Neyrinck Julie Rodriguez Isabelle Massart Jean-Paul Thissen Joshua R. Huot Fabrizio Pin Andrea Bonetto Nathalie M. Delzenne Giulio G. Muccioli Laure B. Bindels |
| author_facet | Morgane M. Thibaut Martin Roumain Edwige Piron Justine Gillard Axelle Loriot Audrey M. Neyrinck Julie Rodriguez Isabelle Massart Jean-Paul Thissen Joshua R. Huot Fabrizio Pin Andrea Bonetto Nathalie M. Delzenne Giulio G. Muccioli Laure B. Bindels |
| author_sort | Morgane M. Thibaut |
| collection | DOAJ |
| description | Alterations in bile acid profile and pathways contribute to hepatic inflammation in cancer cachexia, a syndrome worsening the prognosis of cancer patients. As the gut microbiota impinges on host metabolism through bile acids, the current study aimed to explore the functional contribution of gut microbial dysbiosis to bile acid dysmetabolism and associated disorders in cancer cachexia. Using three mouse models of cancer cachexia (the C26, MC38 and HCT116 models), we evidenced a reduction in the hepatic levels of several secondary bile acids, mainly taurodeoxycholic (TDCA). This reduction in hepatic TDCA occurred before the appearance of cachexia. Longitudinal analysis of the gut microbiota pinpointed an ASV, identified as Xylanibacter rodentium, as a bacterium potentially involved in the reduced production of TDCA. Coherently, stable isotope-based experiments highlighted a robust decrease in the microbial 7α-dehydroxylation (7α-DH) activity with no changes in the bile salt hydrolase (BSH) activity in cachectic mice. This approach also highlighted a reduced microbial 7α-hydroxysteroid dehydrogenase (7α-HSDH) and 12α-hydroxysteroid dehydrogenase (12α-HSDH) activities in these mice. The contribution of the lower production of TDCA to cancer cachexia was explored in vitro and in vivo. In vitro, TDCA prevented myotube atrophy, whereas in vivo hepatic whole transcriptome analysis revealed that TDCA administration to cachectic mice improved the unfolded protein response and cholesterol homeostasis pathways. Coherently, TDCA administration reversed hepatic cholesterol accumulation in these mice. Altogether, this work highlights the contribution of the gut microbiota to bile acid dysmetabolism and the therapeutic interest of the secondary bile acid TDCA for hepatic cholesterol homeostasis in the context of cancer cachexia. Such discovery may prove instrumental in the understanding of other metabolic diseases characterized by microbial dysbiosis. More broadly, our work demonstrates the interest and relevance of microbial activity measurements using stable isotopes, an approach currently underused in the microbiome field. |
| format | Article |
| id | doaj-art-3988e22657af4fec819198909103748a |
| institution | Kabale University |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-3988e22657af4fec819198909103748a2025-01-09T04:50:34ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2449586The microbiota-derived bile acid taurodeoxycholic acid improves hepatic cholesterol levels in mice with cancer cachexiaMorgane M. Thibaut0Martin Roumain1Edwige Piron2Justine Gillard3Axelle Loriot4Audrey M. Neyrinck5Julie Rodriguez6Isabelle Massart7Jean-Paul Thissen8Joshua R. Huot9Fabrizio Pin10Andrea Bonetto11Nathalie M. Delzenne12Giulio G. Muccioli13Laure B. Bindels14Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, BelgiumMetabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, BelgiumMetabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, BelgiumMetabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, BelgiumComputational Biology and Bioinformatics Unit (CBIO), de Duve Institute, UCLouvain, Université catholique de Louvain, Brussels, BelgiumMetabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, BelgiumMetabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, BelgiumEndocrinology, Diabetology and Nutrition Department, Institut de Recherches Expérimentales et Cliniques, UCLouvain, Université catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, BelgiumEndocrinology, Diabetology and Nutrition Department, Institut de Recherches Expérimentales et Cliniques, UCLouvain, Université catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, BelgiumDepartment of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN, USADepartment of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN, USADepartment of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USAMetabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, BelgiumBioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, BelgiumMetabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, BelgiumAlterations in bile acid profile and pathways contribute to hepatic inflammation in cancer cachexia, a syndrome worsening the prognosis of cancer patients. As the gut microbiota impinges on host metabolism through bile acids, the current study aimed to explore the functional contribution of gut microbial dysbiosis to bile acid dysmetabolism and associated disorders in cancer cachexia. Using three mouse models of cancer cachexia (the C26, MC38 and HCT116 models), we evidenced a reduction in the hepatic levels of several secondary bile acids, mainly taurodeoxycholic (TDCA). This reduction in hepatic TDCA occurred before the appearance of cachexia. Longitudinal analysis of the gut microbiota pinpointed an ASV, identified as Xylanibacter rodentium, as a bacterium potentially involved in the reduced production of TDCA. Coherently, stable isotope-based experiments highlighted a robust decrease in the microbial 7α-dehydroxylation (7α-DH) activity with no changes in the bile salt hydrolase (BSH) activity in cachectic mice. This approach also highlighted a reduced microbial 7α-hydroxysteroid dehydrogenase (7α-HSDH) and 12α-hydroxysteroid dehydrogenase (12α-HSDH) activities in these mice. The contribution of the lower production of TDCA to cancer cachexia was explored in vitro and in vivo. In vitro, TDCA prevented myotube atrophy, whereas in vivo hepatic whole transcriptome analysis revealed that TDCA administration to cachectic mice improved the unfolded protein response and cholesterol homeostasis pathways. Coherently, TDCA administration reversed hepatic cholesterol accumulation in these mice. Altogether, this work highlights the contribution of the gut microbiota to bile acid dysmetabolism and the therapeutic interest of the secondary bile acid TDCA for hepatic cholesterol homeostasis in the context of cancer cachexia. Such discovery may prove instrumental in the understanding of other metabolic diseases characterized by microbial dysbiosis. More broadly, our work demonstrates the interest and relevance of microbial activity measurements using stable isotopes, an approach currently underused in the microbiome field.https://www.tandfonline.com/doi/10.1080/19490976.2025.2449586Cancer cachexiabile acidsgut microbiotamuscle atrophyliverXylanibacter |
| spellingShingle | Morgane M. Thibaut Martin Roumain Edwige Piron Justine Gillard Axelle Loriot Audrey M. Neyrinck Julie Rodriguez Isabelle Massart Jean-Paul Thissen Joshua R. Huot Fabrizio Pin Andrea Bonetto Nathalie M. Delzenne Giulio G. Muccioli Laure B. Bindels The microbiota-derived bile acid taurodeoxycholic acid improves hepatic cholesterol levels in mice with cancer cachexia Gut Microbes Cancer cachexia bile acids gut microbiota muscle atrophy liver Xylanibacter |
| title | The microbiota-derived bile acid taurodeoxycholic acid improves hepatic cholesterol levels in mice with cancer cachexia |
| title_full | The microbiota-derived bile acid taurodeoxycholic acid improves hepatic cholesterol levels in mice with cancer cachexia |
| title_fullStr | The microbiota-derived bile acid taurodeoxycholic acid improves hepatic cholesterol levels in mice with cancer cachexia |
| title_full_unstemmed | The microbiota-derived bile acid taurodeoxycholic acid improves hepatic cholesterol levels in mice with cancer cachexia |
| title_short | The microbiota-derived bile acid taurodeoxycholic acid improves hepatic cholesterol levels in mice with cancer cachexia |
| title_sort | microbiota derived bile acid taurodeoxycholic acid improves hepatic cholesterol levels in mice with cancer cachexia |
| topic | Cancer cachexia bile acids gut microbiota muscle atrophy liver Xylanibacter |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2025.2449586 |
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