Comprehensive human amniotic fluid metagenomics supports the sterile womb hypothesis

Han Chen Wang, Gui Xiang Yang, Yuxiang Hu, Patricia Lam, Karan Sangha, Dawn Siciliano, Anne Swenerton, Ruth Miller, Peter Tilley, Peter Von Dadelszen, Shirin Kalyan, Patrick Tang, Millan S. Patel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


As metagenomic approaches for detecting infectious agents have improved, each tissue that was once thought to be sterile has been found to harbor a variety of microorganisms. Controversy still exists over the status of amniotic fluid, which is part of an immunologically privileged zone that is required to prevent maternal immune system rejection of the fetus. Due to this privilege, the exclusion of microbes has been proposed to be mandatory, leading to the sterile womb hypothesis. Since nucleic acid yields from amniotic fluid are very low, contaminating nucleic acid found in water, reagents and the laboratory environment frequently confound attempts to address this hypothesis. Here we present metagenomic criteria for microorganism detection and a metagenomic method able to be performed with small volumes of starting material, while controlling for exogenous contamination, to circumvent these and other pitfalls. We use this method to show that human mid-gestational amniotic fluid has no detectable virome or microbiome, supporting the sterile womb hypothesis.

Original languageEnglish
Article number6875
JournalScientific Reports
Issue number1
Publication statusPublished - Dec 2022


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