Maternal gut microbiota influences immune activation at the maternal-fetal interface affecting pregnancy outcome
Abstract Preeclampsia is a leading cause of morbidity and mortality in pregnant women, affecting 5–8% of gestations worldwide. Its development is influenced by maternal immune abnormalities, metabolic disorders, and gut dysbiosis. In this study, we show that gut dysbiosis in pregnant C57BL/6J dams l...
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58533-8 |
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| author | Silvia Giugliano Andrea Gatti Martina Rusin Tilo Schorn Silvia Pimazzoni Michela Calanni-Pileri Valentina Fraccascia Sara Carloni Maria Rescigno |
| author_facet | Silvia Giugliano Andrea Gatti Martina Rusin Tilo Schorn Silvia Pimazzoni Michela Calanni-Pileri Valentina Fraccascia Sara Carloni Maria Rescigno |
| author_sort | Silvia Giugliano |
| collection | DOAJ |
| description | Abstract Preeclampsia is a leading cause of morbidity and mortality in pregnant women, affecting 5–8% of gestations worldwide. Its development is influenced by maternal immune abnormalities, metabolic disorders, and gut dysbiosis. In this study, we show that gut dysbiosis in pregnant C57BL/6J dams leads to increased fetal resorption, impaired placental development and altered vascularization. These adverse outcomes are associated with key pathological features of preeclampsia, including hypoxia, endoplasmic reticulum (ER) stress and reduction in uterine natural killer (NK) cell numbers. Furthermore, gut dysbiosis significantly perturbs placental carbohydrate metabolism, which impairs NK cell IFN-γ secretion. Notably, glucose supplementation restores placental NK cell function and reduces fetal resorption, suggesting that the observed impairment is reversible and dependent on a lower glycolytic rate. These findings highlight maternal gut microbiota as a key player in carbohydrate metabolism, with a pivotal role in modulating placental immunity and pregnancy outcome. The results provide valuable insights into potential metabolic biomarkers and suggest that targeting the gut microbiota may offer a strategy for preventing preeclampsia. |
| format | Article |
| id | doaj-art-063cc6719b0243c69f2b896a487e4430 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-063cc6719b0243c69f2b896a487e44302025-08-20T01:49:48ZengNature PortfolioNature Communications2041-17232025-05-0116111510.1038/s41467-025-58533-8Maternal gut microbiota influences immune activation at the maternal-fetal interface affecting pregnancy outcomeSilvia Giugliano0Andrea Gatti1Martina Rusin2Tilo Schorn3Silvia Pimazzoni4Michela Calanni-Pileri5Valentina Fraccascia6Sara Carloni7Maria Rescigno8Department of Biomedical Sciences, Humanitas University, Pieve EmanueleIRCCS Humanitas Research HospitalDepartment of Biomedical Sciences, Humanitas University, Pieve EmanueleIRCCS Humanitas Research HospitalIRCCS Humanitas Research HospitalDepartment of Biomedical Sciences, Humanitas University, Pieve EmanueleDepartment of Biomedical Sciences, Humanitas University, Pieve EmanueleDepartment of Biomedical Sciences, Humanitas University, Pieve EmanueleDepartment of Biomedical Sciences, Humanitas University, Pieve EmanueleAbstract Preeclampsia is a leading cause of morbidity and mortality in pregnant women, affecting 5–8% of gestations worldwide. Its development is influenced by maternal immune abnormalities, metabolic disorders, and gut dysbiosis. In this study, we show that gut dysbiosis in pregnant C57BL/6J dams leads to increased fetal resorption, impaired placental development and altered vascularization. These adverse outcomes are associated with key pathological features of preeclampsia, including hypoxia, endoplasmic reticulum (ER) stress and reduction in uterine natural killer (NK) cell numbers. Furthermore, gut dysbiosis significantly perturbs placental carbohydrate metabolism, which impairs NK cell IFN-γ secretion. Notably, glucose supplementation restores placental NK cell function and reduces fetal resorption, suggesting that the observed impairment is reversible and dependent on a lower glycolytic rate. These findings highlight maternal gut microbiota as a key player in carbohydrate metabolism, with a pivotal role in modulating placental immunity and pregnancy outcome. The results provide valuable insights into potential metabolic biomarkers and suggest that targeting the gut microbiota may offer a strategy for preventing preeclampsia.https://doi.org/10.1038/s41467-025-58533-8 |
| spellingShingle | Silvia Giugliano Andrea Gatti Martina Rusin Tilo Schorn Silvia Pimazzoni Michela Calanni-Pileri Valentina Fraccascia Sara Carloni Maria Rescigno Maternal gut microbiota influences immune activation at the maternal-fetal interface affecting pregnancy outcome Nature Communications |
| title | Maternal gut microbiota influences immune activation at the maternal-fetal interface affecting pregnancy outcome |
| title_full | Maternal gut microbiota influences immune activation at the maternal-fetal interface affecting pregnancy outcome |
| title_fullStr | Maternal gut microbiota influences immune activation at the maternal-fetal interface affecting pregnancy outcome |
| title_full_unstemmed | Maternal gut microbiota influences immune activation at the maternal-fetal interface affecting pregnancy outcome |
| title_short | Maternal gut microbiota influences immune activation at the maternal-fetal interface affecting pregnancy outcome |
| title_sort | maternal gut microbiota influences immune activation at the maternal fetal interface affecting pregnancy outcome |
| url | https://doi.org/10.1038/s41467-025-58533-8 |
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