Maternal gut microbiota‐derived daidzein prevents osteoporosis in female offspring following prenatal prednisone exposure
Abstract Prenatal exposure to glucocorticoids is linked to long‐term health risks in offspring, but the role of maternal gut microbiota in mediating these effects remains unclear. Here, we demonstrate that prenatal prednisone therapy (PPT) in humans and prenatal prednisone exposure (PPE) in rats res...
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Wiley
2025-08-01
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| Online Access: | https://doi.org/10.1002/imt2.70037 |
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| author | Chi Ma Hangyuan He Kunpeng Wang Juanjuan Guo Liang Liu Yuting Chen Bin Li Hao Xiao Xufeng Li Xiaoqian Lu Tingting Wang Yinxian Wen Hui Wang Liaobin Chen |
| author_facet | Chi Ma Hangyuan He Kunpeng Wang Juanjuan Guo Liang Liu Yuting Chen Bin Li Hao Xiao Xufeng Li Xiaoqian Lu Tingting Wang Yinxian Wen Hui Wang Liaobin Chen |
| author_sort | Chi Ma |
| collection | DOAJ |
| description | Abstract Prenatal exposure to glucocorticoids is linked to long‐term health risks in offspring, but the role of maternal gut microbiota in mediating these effects remains unclear. Here, we demonstrate that prenatal prednisone therapy (PPT) in humans and prenatal prednisone exposure (PPE) in rats result in sex‐specific long bone dysplasia in offspring, including reduced peak bone mass (PBM) and heightened osteoporosis risk in female offspring. Multi‐omics profiling and fecal microbiota transplantation show that PPE alters maternal gut microbiota composition and depletes the microbial metabolite daidzein (DAI). DAI deficiency suppresses Hoxd12 expression, impairs osteogenesis, and leads to PBM decline in female offspring. In bone marrow‐derived mesenchymal stem cells from PPE female offspring, DAI promoted Hoxd12 expression and osteogenic differentiation. Notably, DAI supplementation restored H3K9ac levels, enhanced Hoxd12 expression, and promoted osteogenic differentiation through the ERβ/KAT6A pathway. Furthermore, maternal DAI supplementation during pregnancy prevented osteoporosis susceptibility in PPE female offspring and alleviated functional abnormalities in multiple organs, including the liver, hippocampus, ovary, and adrenal gland. In conclusion, PPE induces multiorgan dysplasia and increases disease predisposition (e.g., osteoporosis) in female offspring by disrupting maternal gut microbiota and depleting DAI. Maternal DAI supplementation provides a promising preventive strategy to counteract these adverse outcomes. |
| format | Article |
| id | doaj-art-9b92d920194f4eb99855d1459a3f6ba2 |
| institution | Kabale University |
| issn | 2770-596X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | iMeta |
| spelling | doaj-art-9b92d920194f4eb99855d1459a3f6ba22025-08-22T08:13:03ZengWileyiMeta2770-596X2025-08-0144n/an/a10.1002/imt2.70037Maternal gut microbiota‐derived daidzein prevents osteoporosis in female offspring following prenatal prednisone exposureChi Ma0Hangyuan He1Kunpeng Wang2Juanjuan Guo3Liang Liu4Yuting Chen5Bin Li6Hao Xiao7Xufeng Li8Xiaoqian Lu9Tingting Wang10Yinxian Wen11Hui Wang12Liaobin Chen13Department of Orthopedic Surgery Division of Joint Surgery and Sports Medicine, Zhongnan Hospital of Wuhan University Wuhan ChinaDepartment of Orthopedic Surgery Division of Joint Surgery and Sports Medicine, Zhongnan Hospital of Wuhan University Wuhan ChinaDepartment of Obstetrics and Gynaecology Wuhan Hospital of Traditional Chinese Medicine Wuhan ChinaHubei Provincial Key Laboratory of Developmentally Originated Diseases Wuhan ChinaDepartment of Orthopedic Surgery Division of Joint Surgery and Sports Medicine, Zhongnan Hospital of Wuhan University Wuhan ChinaHubei Provincial Key Laboratory of Developmentally Originated Diseases Wuhan ChinaDepartment of Orthopedic Surgery Division of Joint Surgery and Sports Medicine, Zhongnan Hospital of Wuhan University Wuhan ChinaDepartment of Orthopedic Surgery Division of Joint Surgery and Sports Medicine, Zhongnan Hospital of Wuhan University Wuhan ChinaDepartment of Orthopedic Surgery Division of Joint Surgery and Sports Medicine, Zhongnan Hospital of Wuhan University Wuhan ChinaDepartment of Pharmacology Basic Medical School of Wuhan University Wuhan ChinaDepartment of Pharmacology Basic Medical School of Wuhan University Wuhan ChinaDepartment of Orthopedic Surgery Division of Joint Surgery and Sports Medicine, Zhongnan Hospital of Wuhan University Wuhan ChinaDepartment of Pharmacology Basic Medical School of Wuhan University Wuhan ChinaDepartment of Orthopedic Surgery Division of Joint Surgery and Sports Medicine, Zhongnan Hospital of Wuhan University Wuhan ChinaAbstract Prenatal exposure to glucocorticoids is linked to long‐term health risks in offspring, but the role of maternal gut microbiota in mediating these effects remains unclear. Here, we demonstrate that prenatal prednisone therapy (PPT) in humans and prenatal prednisone exposure (PPE) in rats result in sex‐specific long bone dysplasia in offspring, including reduced peak bone mass (PBM) and heightened osteoporosis risk in female offspring. Multi‐omics profiling and fecal microbiota transplantation show that PPE alters maternal gut microbiota composition and depletes the microbial metabolite daidzein (DAI). DAI deficiency suppresses Hoxd12 expression, impairs osteogenesis, and leads to PBM decline in female offspring. In bone marrow‐derived mesenchymal stem cells from PPE female offspring, DAI promoted Hoxd12 expression and osteogenic differentiation. Notably, DAI supplementation restored H3K9ac levels, enhanced Hoxd12 expression, and promoted osteogenic differentiation through the ERβ/KAT6A pathway. Furthermore, maternal DAI supplementation during pregnancy prevented osteoporosis susceptibility in PPE female offspring and alleviated functional abnormalities in multiple organs, including the liver, hippocampus, ovary, and adrenal gland. In conclusion, PPE induces multiorgan dysplasia and increases disease predisposition (e.g., osteoporosis) in female offspring by disrupting maternal gut microbiota and depleting DAI. Maternal DAI supplementation provides a promising preventive strategy to counteract these adverse outcomes.https://doi.org/10.1002/imt2.70037daidzeinDOHaDmaternal gut microbiotaosteoporosisprenatal prednisone exposure |
| spellingShingle | Chi Ma Hangyuan He Kunpeng Wang Juanjuan Guo Liang Liu Yuting Chen Bin Li Hao Xiao Xufeng Li Xiaoqian Lu Tingting Wang Yinxian Wen Hui Wang Liaobin Chen Maternal gut microbiota‐derived daidzein prevents osteoporosis in female offspring following prenatal prednisone exposure iMeta daidzein DOHaD maternal gut microbiota osteoporosis prenatal prednisone exposure |
| title | Maternal gut microbiota‐derived daidzein prevents osteoporosis in female offspring following prenatal prednisone exposure |
| title_full | Maternal gut microbiota‐derived daidzein prevents osteoporosis in female offspring following prenatal prednisone exposure |
| title_fullStr | Maternal gut microbiota‐derived daidzein prevents osteoporosis in female offspring following prenatal prednisone exposure |
| title_full_unstemmed | Maternal gut microbiota‐derived daidzein prevents osteoporosis in female offspring following prenatal prednisone exposure |
| title_short | Maternal gut microbiota‐derived daidzein prevents osteoporosis in female offspring following prenatal prednisone exposure |
| title_sort | maternal gut microbiota derived daidzein prevents osteoporosis in female offspring following prenatal prednisone exposure |
| topic | daidzein DOHaD maternal gut microbiota osteoporosis prenatal prednisone exposure |
| url | https://doi.org/10.1002/imt2.70037 |
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