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 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,

SUBMITTER: Ma C 

PROVIDER: S-EPMC12371263 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature