Comprehensive human amniotic fluid metagenomics supports the sterile womb hypothesis

TY - JOUR

T1 - Comprehensive human amniotic fluid metagenomics supports the sterile womb hypothesis

AU - Wang, Han Chen

AU - Yang, Gui Xiang

AU - Hu, Yuxiang

AU - Lam, Patricia

AU - Sangha, Karan

AU - Siciliano, Dawn

AU - Swenerton, Anne

AU - Miller, Ruth

AU - Tilley, Peter

AU - Von Dadelszen, Peter

AU - Kalyan, Shirin

AU - Tang, Patrick

AU - Patel, Millan S.

N1 - Funding Information: The authors thank Drs. John Brunstein, John Taylor, Ricardo Flores Pedauye, Yongjun Zhao, Robert Holt, Alexandre Montpetit, Jan Friedman, Fiona Brinkman, Michael Peabody and Thea Van Rossum for providing advice and reagents during the course of this study. We are indebted to the IDIBAPS Biobank, integrated in the Spanish National Biobank Network, for positive control samples. This work was funded by CIHR operating grant #130494 and by BC Children’s Hospital Foundation Telethon #KRZ28015 and Circle of Care #KRZ75069 grants. The non-human reads from amniotic fluid samples tested in this study are available on NCBI SRA under BioProject PRJNA766590. Pathogen databases and all Python and Excel scripts developed for this study are available upon request. Funding Information: This study was supported by CIHR operating grant #130494 and by BC Children’s Hospital Foundation Telethon #KRZ28015 and Circle of Care #KRZ75069 grants. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85128876679&partnerID=8YFLogxK

U2 - 10.1038/s41598-022-10869-7

DO - 10.1038/s41598-022-10869-7

M3 - Article

C2 - 35477737

AN - SCOPUS:85128876679

SN - 2045-2322

VL - 12

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 6875

ER -