IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-58533-8.html
   My bibliography  Save this article

Maternal gut microbiota influences immune activation at the maternal-fetal interface affecting pregnancy outcome

Author

Listed:
  • Silvia Giugliano

    (Pieve Emanuele
    IRCCS Humanitas Research Hospital)

  • Andrea Gatti

    (IRCCS Humanitas Research Hospital
    University of Milan)

  • Martina Rusin

    (Pieve Emanuele
    IRCCS Humanitas Research Hospital)

  • Tilo Schorn

    (IRCCS Humanitas Research Hospital)

  • Silvia Pimazzoni

    (IRCCS Humanitas Research Hospital)

  • Michela Calanni-Pileri

    (Pieve Emanuele
    IRCCS Humanitas Research Hospital)

  • Valentina Fraccascia

    (Pieve Emanuele
    IRCCS Humanitas Research Hospital)

  • Sara Carloni

    (Pieve Emanuele
    IRCCS Humanitas Research Hospital)

  • Maria Rescigno

    (Pieve Emanuele
    IRCCS Humanitas Research Hospital)

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.

Suggested Citation

  • Silvia Giugliano & Andrea Gatti & Martina Rusin & Tilo Schorn & Silvia Pimazzoni & Michela Calanni-Pileri & Valentina Fraccascia & Sara Carloni & Maria Rescigno, 2025. "Maternal gut microbiota influences immune activation at the maternal-fetal interface affecting pregnancy outcome," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58533-8
    DOI: 10.1038/s41467-025-58533-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-58533-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-58533-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Mevik, Björn-Helge & Wehrens, Ron, 2007. "The pls Package: Principal Component and Partial Least Squares Regression in R," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 18(i02).
    2. Chris Schiering & Emma Wincent & Amina Metidji & Andrea Iseppon & Ying Li & Alexandre J. Potocnik & Sara Omenetti & Colin J. Henderson & C. Roland Wolf & Daniel W. Nebert & Brigitta Stockinger, 2017. "Feedback control of AHR signalling regulates intestinal immunity," Nature, Nature, vol. 542(7640), pages 242-245, February.
    3. Elaine Holmes & Ruey Leng Loo & Jeremiah Stamler & Magda Bictash & Ivan K. S. Yap & Queenie Chan & Tim Ebbels & Maria De Iorio & Ian J. Brown & Kirill A. Veselkov & Martha L. Daviglus & Hugo Kesteloot, 2008. "Human metabolic phenotype diversity and its association with diet and blood pressure," Nature, Nature, vol. 453(7193), pages 396-400, May.
    4. Peter J. Turnbaugh & Ruth E. Ley & Micah Hamady & Claire M. Fraser-Liggett & Rob Knight & Jeffrey I. Gordon, 2007. "The Human Microbiome Project," Nature, Nature, vol. 449(7164), pages 804-810, October.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Shilan Li & Jianxin Shi & Paul Albert & Hong-Bin Fang, 2022. "Dependence Structure Analysis and Its Application in Human Microbiome," Mathematics, MDPI, vol. 11(1), pages 1-14, December.
    2. Jae-Chang Cho, 2021. "Human microbiome privacy risks associated with summary statistics," PLOS ONE, Public Library of Science, vol. 16(4), pages 1-11, April.
    3. Pirjo Wacklin & Harri Mäkivuokko & Noora Alakulppi & Janne Nikkilä & Heli Tenkanen & Jarkko Räbinä & Jukka Partanen & Kari Aranko & Jaana Mättö, 2011. "Secretor Genotype (FUT2 gene) Is Strongly Associated with the Composition of Bifidobacteria in the Human Intestine," PLOS ONE, Public Library of Science, vol. 6(5), pages 1-10, May.
    4. Elton Mammadov & Michael Denk & Frank Riedel & Cezary Kaźmierowski & Karolina Lewinska & Remigiusz Łukowiak & Witold Grzebisz & Amrakh I. Mamedov & Cornelia Glaesser, 2022. "Determination of Mehlich 3 Extractable Elements with Visible and Near Infrared Spectroscopy in a Mountainous Agricultural Land, the Caucasus Mountains," Land, MDPI, vol. 11(3), pages 1-24, March.
    5. Giacomo Crucil & Fabio Castaldi & Emilien Aldana-Jague & Bas van Wesemael & Andy Macdonald & Kristof Van Oost, 2019. "Assessing the Performance of UAS-Compatible Multispectral and Hyperspectral Sensors for Soil Organic Carbon Prediction," Sustainability, MDPI, vol. 11(7), pages 1-18, March.
    6. Disha Tandon & Mohammed Monzoorul Haque & Sharmila S Mande, 2016. "Inferring Intra-Community Microbial Interaction Patterns from Metagenomic Datasets Using Associative Rule Mining Techniques," PLOS ONE, Public Library of Science, vol. 11(4), pages 1-16, April.
    7. Bennett, Donyetta & Mekelburg, Erik & Strauss, Jack & Williams, T.H., 2024. "Unlocking the black box of sentiment and cryptocurrency: What, which, why, when and how?," Global Finance Journal, Elsevier, vol. 60(C).
    8. Chantrell J G Frazier & Vidia A Gokool & Howard K Holness & DeEtta K Mills & Kenneth G Furton, 2023. "Multivariate regression modelling for gender prediction using volatile organic compounds from hand odor profiles via HS-SPME-GC-MS," PLOS ONE, Public Library of Science, vol. 18(7), pages 1-12, July.
    9. Eslami, Seyed Pouyan & Ghasemaghaei, Maryam, 2018. "Effects of online review positiveness and review score inconsistency on sales: A comparison by product involvement," Journal of Retailing and Consumer Services, Elsevier, vol. 45(C), pages 74-80.
    10. Tomasz Rymarczyk & Krzysztof Król & Edward Kozłowski & Tomasz Wołowiec & Marta Cholewa-Wiktor & Piotr Bednarczuk, 2021. "Application of Electrical Tomography Imaging Using Machine Learning Methods for the Monitoring of Flood Embankments Leaks," Energies, MDPI, vol. 14(23), pages 1-35, December.
    11. Shinji Fukuda & Yumiko Nakanishi & Eisuke Chikayama & Hiroshi Ohno & Tsuneo Hino & Jun Kikuchi, 2009. "Evaluation and Characterization of Bacterial Metabolic Dynamics with a Novel Profiling Technique, Real-Time Metabolotyping," PLOS ONE, Public Library of Science, vol. 4(3), pages 1-10, March.
    12. Robert Pater & Łukasz Cywiński & Ruslan Harasym & Kazimierz Tarchalski, 2018. "Intangible capital and the economic growth in Poland," Bank i Kredyt, Narodowy Bank Polski, vol. 49(2), pages 93-114.
    13. Natallia Pashkevich & Darek Haftor & Mikael Karlsson & Soumitra Chowdhury, 2019. "Sustainability through the Digitalization of Industrial Machines: Complementary Factors of Fuel Consumption and Productivity for Forklifts with Sensors," Sustainability, MDPI, vol. 11(23), pages 1-21, November.
    14. Ran Li & Yongming Wang & Han Hu & Yan Tan & Yingfei Ma, 2022. "Metagenomic analysis reveals unexplored diversity of archaeal virome in the human gut," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    15. Charlotte Höpker & Klaus Dittert & Hans-Werner Olfs, 2025. "On-Farm Application of Near-Infrared Spectroscopy for the Determination of Nutrients in Liquid Organic Manures: Challenges and Opportunities," Agriculture, MDPI, vol. 15(2), pages 1-15, January.
    16. Zhao, Ting & Yang, Zhenshan, 2017. "Towards green growth and management: Relative efficiency and gaps of Chinese cities," Renewable and Sustainable Energy Reviews, Elsevier, vol. 80(C), pages 481-494.
    17. Miles Grafton & Therese Kaul & Alan Palmer & Peter Bishop & Michael White, 2019. "Technical Note: Regression Analysis of Proximal Hyperspectral Data to Predict Soil pH and Olsen P," Agriculture, MDPI, vol. 9(3), pages 1-18, March.
    18. Tanin Sirimongkolkasem & Reza Drikvandi, 2019. "On Regularisation Methods for Analysis of High Dimensional Data," Annals of Data Science, Springer, vol. 6(4), pages 737-763, December.
    19. Barbara Emmenegger & Julien Massoni & Christine M. Pestalozzi & Miriam Bortfeld-Miller & Benjamin A. Maier & Julia A. Vorholt, 2023. "Identifying microbiota community patterns important for plant protection using synthetic communities and machine learning," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    20. Margaret Coleman & Christopher Elkins & Bradford Gutting & Emmanuel Mongodin & Gloria Solano‐Aguilar & Isabel Walls, 2018. "Microbiota and Dose Response: Evolving Paradigm of Health Triangle," Risk Analysis, John Wiley & Sons, vol. 38(10), pages 2013-2028, October.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58533-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.