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

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

Publications: Contribution to journalArticlePeer Reviewed


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.

Original languageEnglish
Pages (from-to)639-649
Number of pages11
Issue number7945
Publication statusPublished - 26 Jan 2023

Austrian Fields of Science 2012

  • 106026 Ecosystem research
  • 106022 Microbiology
  • 106059 Microbiome research


  • Animals
  • Female
  • Humans
  • Pregnancy
  • Amniotic Fluid/immunology
  • Biomass
  • Mammals
  • Microbiota/genetics
  • Placenta/immunology
  • Fetus/immunology
  • DNA Contamination
  • Reproducibility of Results

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