Human Microbiome Action
Published January 25, 2023 | Version v1
Journal article Open

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

Creators

  • 1. McMaster University, Canada
  • 2. University of Amsterdam, The Netherlands
  • 3. University of Alberta, Canada
  • 4. University of Calgary, Canada
  • 5. University of Gothenburg, Sweden
  • 6. European Molecular Biology Laboratory, Germany
  • 7. Charité Universitätsmedizin Berlin, Germany
  • 8. University of Pensylvania, USA
  • 9. University Paris Saclay - Inrae, France
  • 10. University of Helsinki, Finland
  • 11. Broad Institute of MIT and Harvard, USA
  • 12. University of California Davis, USA
  • 13. University of Bern, Switzerland
  • 14. University of ALberta, Canada
  • 15. Harvard Chan School of Public Health, USA
  • 16. Quadram Institute Bioscience, UK
  • 17. University Hospital Aachen, Germany
  • 18. Yale School of Medicine, USA
  • 19. University of Antwerp, Belgium
  • 20. University College Cork, Ireland
  • 21. Helmholz Centre for Infection Research, Germany
  • 22. Bar-Ilan University, Israel
  • 23. Welcome Sanger Institute, UK
  • 24. Max Planck Institute for Developmental Biology, Germany
  • 25. University of Chicago, USA
  • 26. University of Cambridge, UK
  • 27. VIB Center for Microbiology, Belgium
  • 28. University of Vienna, Austria
  • 29. Weizmann Institute of Science, Israel
  • 30. University of Trento, Italy
  • 31. Sorbonne Université - Inserm, Paris
  • 32. Kings College London, UK
  • 33. University of Otago, New Zealand
  • 34. University of Aberdeen, UK
  • 35. Hebrew University of Jerusalem, Israel

Description

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 to be 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.

Files

2023 Kennedy Nat---_Questioning the fetal microbiome_Proofs.pdf

Files (2.0 MB)

Additional details

Funding

IHMCSA – International Human Microbiome Coordination and Support Action 964590
European Commission
Homo.symbiosus – Assessing, preserving and restoring man-microbes symbiosis 788191
European Commission

Dates

Accepted
2023-01-25
Perspective