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

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Kennedy, Katherine M  ORCID logo
de Goffau, Marcus C  ORCID logo
Perez-Muñoz, Maria Elisa  ORCID logo
Arrieta, Marie-Claire  ORCID logo
Bäckhed, Fredrik 


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.



Animals, Female, Humans, Pregnancy, Amniotic Fluid, Biomass, Mammals, Microbiota, Placenta, Fetus, DNA Contamination, Reproducibility of Results

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Springer Science and Business Media LLC
Medical Research Council (MR/K021133/1)
European Commission Horizon 2020 (H2020) Societal Challenges (825410)
Wellcome Trust (100974/B/13/Z)
G.C.S.S. acknowledges funding from Medical Research Council (UK; MR/K021133/1) and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (Women’s Health theme).