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Cited by 371

The DOI matches its Crossref record; 134 of the 134 references it cites were found in a registry or an index.

Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies

Open access
Kennedy, Katherine M., de Goffau, Marcus C., Perez-Muñoz, Maria Elisa, Arrieta, Marie-Claire, Bäckhed, Fredrik, Bork, Peer, Braun, Thorsten, Bushman, Frederic D., Dore, Joel, de Vos, Willem M., Earl, Ashlee M., Eisen, Jonathan A., Elovitz, Michal A., Ganal-Vonarburg, Stephanie C., Gänzle, Michael G., Garrett, Wendy S., Hall, Lindsay J., Hornef, Mathias W., Huttenhower, Curtis, Konnikova, Liza, Lebeer, Sarah, Macpherson, Andrew J., Massey, Ruth C., McHardy, Alice Carolyn, Koren, Omry, Lawley, Trevor D., Ley, Ruth E., O’Mahony, Liam, O’Toole, Paul W., Pamer, Eric G., Parkhill, Julian, Raes, Jeroen, Rattei, Thomas, Salonen, Anne, Segal, Eran, Segata, Nicola, Shanahan, Fergus, Sloboda, Deborah M., Smith, Gordon C. S., Sokol, Harry, Spector, Tim D., Surette, Michael G., Tannock, Gerald W., Walker, Alan W., Yassour, Moran, Walter, Jens·2023·Nature
DOI 10.1038/s41586-022-05546-8
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Abstract

Whether the human fetus and the prenatal intrauterine environment (amniotic fluid and placenta) are stably colonized by microbial communities in a healthy pregnancy remains a subject of debate. Here we evaluate recent studies that characterized microbial populations in human fetuses from the perspectives of reproductive biology, microbial ecology, bioinformatics, immunology, clinical microbiology and gnotobiology, and assess possible mechanisms by which the fetus might interact with microorganisms. Our analysis indicates that the detected microbial signals are likely the result of contamination during the clinical procedures to obtain fetal samples or during DNA extraction and DNA sequencing. Furthermore, the existence of live and replicating microbial populations in healthy fetal tissues is not compatible with fundamental concepts of immunology, clinical microbiology and the derivation of germ-free mammals. These conclusions are important to our understanding of human immune development and illustrate common pitfalls in the microbial analyses of many other low-biomass environments. The pursuit of a fetal microbiome serves as a cautionary example of the challenges of sequence-based microbiome studies when biomass is low or absent, and emphasizes the need for a trans-disciplinary approach that goes beyond contamination controls by also incorporating biological, ecological and mechanistic concepts. This Perspective reviews the evidence for and against the existence of a fetal microbiome and concludes that detected microbial signals are most likely the result of contamination, suggesting that the ‘sterile womb’ hypothesis is correct.

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Metadata

Authors
Kennedy, K. M., de Goffau, M. C., Perez-Muñoz, M. E., Arrieta, M.-C., Bäckhed, F., Bork, P., Braun, T., Bushman, F. D., Dore, J., de Vos, W. M., Earl, A. M., Eisen, J. A., Elovitz, M. A., Ganal-Vonarburg, S. C., Gänzle, M. G., Garrett, W. S., Hall, L. J., Hornef, M. W., Huttenhower, C., Konnikova, L., Lebeer, S., Macpherson, A. J., Massey, R. C., McHardy, A. C., Koren, O., Lawley, T. D., Ley, R. E., O’Mahony, L., O’Toole, P. W., Pamer, E. G., Parkhill, J., Raes, J., Rattei, T., Salonen, A., Segal, E., Segata, N., Shanahan, F., Sloboda, D. M., Smith, G. C. S., Sokol, H., Spector, T. D., Surette, M. G., Tannock, G. W., Walker, A. W., Yassour, M., & Walter, J.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2023-01-25
Volume
613
Issue
7945
Pages
639-649
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-022-05546-8
OpenAlex
W4317951846
Cited by
371
References
134
FWCI
28.09
Type
journal article
Language
en
Open access
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CoChat. (2026). Citation check: Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies. https://app.cochat.ai/papers/10.1038/s41586-022-05546-8
The paper
Kennedy, K. M., de Goffau, M. C., Perez-Muñoz, M. E., Arrieta, M.-C., Bäckhed, F., Bork, P., Braun, T., Bushman, F. D., Dore, J., de Vos, W. M., Earl, A. M., Eisen, J. A., Elovitz, M. A., Ganal-Vonarburg, S. C., Gänzle, M. G., Garrett, W. S., Hall, L. J., Hornef, M. W., Huttenhower, C., . . . Walter, J. (2023). Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies. Nature. https://doi.org/10.1038/s41586-022-05546-8

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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.