Maternal gut microbiota‐derived daidzein prevents osteoporosis in female offspring following prenatal prednisone exposure Article Swipe
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
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1002/imt2.70037
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1002/imt2.70037
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.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/imt2.70037
- https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/imt2.70037
- OA Status
- gold
- References
- 63
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4409959686
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4409959686Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1002/imt2.70037Digital Object Identifier
- Title
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Maternal gut microbiota‐derived daidzein prevents osteoporosis in female offspring following prenatal prednisone exposureWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-04-28Full publication date if available
- Authors
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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 ChenList of authors in order
- Landing page
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https://doi.org/10.1002/imt2.70037Publisher landing page
- PDF URL
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/imt2.70037Direct link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/imt2.70037Direct OA link when available
- Concepts
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Offspring, Osteoporosis, Medicine, Gut flora, Pregnancy, Internal medicine, Endocrinology, Fetus, Physiology, Immunology, Biology, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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63Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.the | 14, 80, 131, 155 |
| abstract_inverted_index.DAI. | 184 |
| abstract_inverted_index.bone | 47, 54, 101 |
| abstract_inverted_index.from | 106 |
| abstract_inverted_index.long | 46 |
| abstract_inverted_index.mass | 55 |
| abstract_inverted_index.peak | 53 |
| abstract_inverted_index.rats | 42 |
| abstract_inverted_index.risk | 60 |
| abstract_inverted_index.role | 15 |
| abstract_inverted_index.show | 70 |
| abstract_inverted_index.stem | 104 |
| abstract_inverted_index.that | 29, 71 |
| abstract_inverted_index.(PBM) | 56 |
| abstract_inverted_index.(PPE) | 40 |
| abstract_inverted_index.(PPT) | 33 |
| abstract_inverted_index.Here, | 26 |
| abstract_inverted_index.cells | 105 |
| abstract_inverted_index.fecal | 67 |
| abstract_inverted_index.leads | 93 |
| abstract_inverted_index.risks | 10 |
| abstract_inverted_index.these | 22, 195 |
| abstract_inverted_index.(DAI). | 84 |
| abstract_inverted_index.(e.g., | 172 |
| abstract_inverted_index.H3K9ac | 121 |
| abstract_inverted_index.Hoxd12 | 88, 112, 124 |
| abstract_inverted_index.alters | 73 |
| abstract_inverted_index.during | 138 |
| abstract_inverted_index.female | 62, 98, 108, 145, 175 |
| abstract_inverted_index.gland. | 161 |
| abstract_inverted_index.health | 9 |
| abstract_inverted_index.humans | 35 |
| abstract_inverted_index.linked | 6 |
| abstract_inverted_index.liver, | 156 |
| abstract_inverted_index.ovary, | 158 |
| abstract_inverted_index.result | 43 |
| abstract_inverted_index.adrenal | 160 |
| abstract_inverted_index.adverse | 196 |
| abstract_inverted_index.decline | 96 |
| abstract_inverted_index.disease | 170 |
| abstract_inverted_index.effects | 23 |
| abstract_inverted_index.impairs | 90 |
| abstract_inverted_index.induces | 165 |
| abstract_inverted_index.levels, | 122 |
| abstract_inverted_index.organs, | 153 |
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| abstract_inverted_index.remains | 24 |
| abstract_inverted_index.therapy | 32 |
| abstract_inverted_index.through | 130 |
| abstract_inverted_index.Abstract | 0 |
| abstract_inverted_index.Maternal | 185 |
| abstract_inverted_index.Notably, | 117 |
| abstract_inverted_index.Prenatal | 1 |
| abstract_inverted_index.daidzein | 83 |
| abstract_inverted_index.depletes | 79 |
| abstract_inverted_index.enhanced | 123 |
| abstract_inverted_index.exposure | 2, 39 |
| abstract_inverted_index.maternal | 17, 74, 135, 179 |
| abstract_inverted_index.multiple | 152 |
| abstract_inverted_index.pathway. | 133 |
| abstract_inverted_index.prenatal | 30, 37 |
| abstract_inverted_index.promoted | 111, 127 |
| abstract_inverted_index.provides | 188 |
| abstract_inverted_index.restored | 120 |
| abstract_inverted_index.strategy | 192 |
| abstract_inverted_index.unclear. | 25 |
| abstract_inverted_index.depleting | 183 |
| abstract_inverted_index.dysplasia | 48, 167 |
| abstract_inverted_index.including | 51, 154 |
| abstract_inverted_index.increases | 169 |
| abstract_inverted_index.mediating | 21 |
| abstract_inverted_index.microbial | 81 |
| abstract_inverted_index.offspring | 146, 176 |
| abstract_inverted_index.outcomes. | 197 |
| abstract_inverted_index.pregnancy | 139 |
| abstract_inverted_index.prevented | 140 |
| abstract_inverted_index.profiling | 65 |
| abstract_inverted_index.promising | 190 |
| abstract_inverted_index.ERβ/KAT6A | 132 |
| abstract_inverted_index.alleviated | 148 |
| abstract_inverted_index.counteract | 194 |
| abstract_inverted_index.deficiency | 86 |
| abstract_inverted_index.disrupting | 178 |
| abstract_inverted_index.expression | 113 |
| abstract_inverted_index.functional | 149 |
| abstract_inverted_index.heightened | 58 |
| abstract_inverted_index.metabolite | 82 |
| abstract_inverted_index.microbiota | 19, 68, 76, 181 |
| abstract_inverted_index.multiorgan | 166 |
| abstract_inverted_index.offspring, | 12, 50, 109 |
| abstract_inverted_index.offspring. | 63, 99 |
| abstract_inverted_index.osteogenic | 115, 128 |
| abstract_inverted_index.prednisone | 31, 38 |
| abstract_inverted_index.preventive | 191 |
| abstract_inverted_index.suppresses | 87 |
| abstract_inverted_index.composition | 77 |
| abstract_inverted_index.conclusion, | 163 |
| abstract_inverted_index.demonstrate | 28 |
| abstract_inverted_index.expression, | 89, 125 |
| abstract_inverted_index.long‐term | 8 |
| abstract_inverted_index.mesenchymal | 103 |
| abstract_inverted_index.Furthermore, | 134 |
| abstract_inverted_index.hippocampus, | 157 |
| abstract_inverted_index.osteoporosis | 59, 141 |
| abstract_inverted_index.Multi‐omics | 64 |
| abstract_inverted_index.abnormalities | 150 |
| abstract_inverted_index.osteogenesis, | 91 |
| abstract_inverted_index.osteoporosis) | 173 |
| abstract_inverted_index.predisposition | 171 |
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| abstract_inverted_index.susceptibility | 142 |
| abstract_inverted_index.differentiation | 129 |
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| abstract_inverted_index.supplementation | 119, 137, 187 |
| abstract_inverted_index.transplantation | 69 |
| abstract_inverted_index.differentiation. | 116 |
| abstract_inverted_index.marrow‐derived | 102 |
| cited_by_percentile_year | |
| countries_distinct_count | 1 |
| institutions_distinct_count | 14 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.699999988079071 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.17131318 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |