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  • Review Article
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The maternal gut microbiome in pregnancy: implications for the developing immune system

Nature Reviews Gastroenterology & Hepatology volume 21, pages 35–45 (2024)Cite this article

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Abstract

The gut microbiome has important roles in host metabolism and immunity, and microbial dysbiosis affects human physiology and health. Maternal immunity and microbial metabolites during pregnancy, microbial transfer during birth, and transfer of immune factors, microorganisms and metabolites via breastfeeding provide critical sources of early-life microbial and immune training, with important consequences for human health. Only a few studies have directly examined the interactions between the gut microbiome and the immune system during pregnancy, and the subsequent effect on offspring development. In this Review, we aim to describe how the maternal microbiome shapes overall pregnancy-associated maternal, fetal and early neonatal immune systems, focusing on the existing evidence and highlighting current gaps to promote further research.

Key points

  • Microbiota–host interactions during pregnancy are key for maternal and neonatal health outcomes and healthy offspring development.

  • Little is known regarding how the maternal microbiota and metabolites shape the maternal–fetal immune system during pregnancy.

  • Limited information is available on the factors that contribute to maternal microbiota–immune system feedback during pregnancy and early lactation.

  • Prenatal and postnatal immune system–microbiome interactions are relevant for human health.

  • The role of breast milk compounds in neonatal immune system development and microbial assembly warrants further studies.

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Fig. 1: Microbial metabolites from the maternal microbiome contribute to fetal and neonatal immune development.
Fig. 2: Human milk microorganisms and their metabolites support the gut microbiome and immune system in the offspring.

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Acknowledgements

The authors thank R. Michita and S. Turjeman for their valuable input. Much appreciation to C. Eke for his contributions to the original version of the Figures. O.K. is supported by the European Research Council Consolidator grant (grant agreement no. 101001355). I.U.M. is supported by NIH/NICHD grant R01 HD091218 and 3R01HD091218-04S1(RADx-UP Supplement). O.K. and M.C.C. acknowledge the support by Biostime Institute Nutrition and Care (BINC) grant. L.K. is supported by Yale University pilot funds, Binational Science Foundation (2019075), and the National Institutes of Health (R21TR002639, R21HD102565, R01DK129552 and R01AI171980). P.B. is supported by grants from Knut and Alice Wallenberg Foundation (2019.0181), Svenska sällskapet för Medicinsk forskning, SSMF (CG-22-0148-H-02), the Swedish Research council (2019-01495, 2022-01567), EU Horizon project grant UNDINE (grant agreement: 101057100) and Wellcome Trust Discovery award (226507/Z/22/Z). M.C.C. was supported by a European Research Council Starting grant (grant agreement no. 639226), the Spanish Ministry of Science and Innovation (grant ref. PID2022-139475OB-I00), PROMETEO GVA (ref. 2020/012) and also from the Horizon Europe Program (INITIALISE- 101094099 project). M.C.C. also acknowledges the Spanish government MCIN/AEI to the Center of Excellence Accreditation Severo Ochoa (CEX2021-001189-S/ MCIN/AEI / 10.13039/501100011033).

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Author notes

  1. These authors contributed equally: Omry Koren, Liza Konnikova, Petter Brodin, Indira U. Mysorekar, Maria Carmen Collado.

Authors and Affiliations

  1. Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel

    Omry Koren

  2. Department of Paediatrics and Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA

    Liza Konnikova

  3. Department of Immunology and Inflammation, Imperial College London, London, UK

    Petter Brodin

  4. Department of Women’s and Children’s Health, Karolinska Institutet, Solna, Sweden

    Petter Brodin

  5. Department of Medicine, Section of Infectious Diseases, Baylor College of Medicine, Houston, TX, USA

    Indira U. Mysorekar

  6. Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA

    Indira U. Mysorekar

  7. Institute of Agrochemistry and Food Technology-National Research Council (IATA-CSIC), Valencia, Spain

    Maria Carmen Collado

Authors
  1. Omry Koren
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Contributions

The authors contributed equally to all aspects of the manuscript.

Corresponding author

Correspondence to Maria Carmen Collado.

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Competing interests

O.K. is a co-founder of Shela Accurate Diagnosis LTD (Israel). I.U.M. serves on the scientific advisory board of Luca Biologics. P.B. serves on the scientific advisory board of Pixelgen Technologies AB (Sweden), Oxford Immune Algorithmics (UK), and Scailyte AG (Switzerland) and is an executive board member of Kancera AB (Sweden) and co-founder of Cytodelics AB (Sweden). The other authors declare no competing interests.

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Nature Reviews Gastroenterology & Hepatology thanks Nardhy Gomez-Lopez and Gérard Eberl for their contribution to the peer review of this work.

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Koren, O., Konnikova, L., Brodin, P. et al. The maternal gut microbiome in pregnancy: implications for the developing immune system. Nat Rev Gastroenterol Hepatol 21, 35–45 (2024). https://doi.org/10.1038/s41575-023-00864-2

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