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Abstract

It is widely recognized that pathogens can be transmitted across the placenta from mother to foetus. Recent re-evaluation of metagenomic studies indicates that the placenta has no unique microbiome of commensal bacteria. However, viral transmission across the placenta, including transmission of DNA viruses such as the human herpesviruses, is possible. A fuller understanding of which DNA virus sequence can be found in the placenta is required. We employed a metagenomic analysis to identify viral DNA sequences in placental metagenomes from full-term births (20 births), pre-term births (13 births), births from pregnancies associated with antenatal infections (12 births) or pre-term births with antenatal infections (three births). Our analysis found only a small number of DNA sequences corresponding to the genomes of human herpesviruses in four of the 48 metagenomes analysed. Therefore, our data suggest that DNA virus infection of the placenta is rare and support the concept that the placenta is largely free of pathogen infection.

Funding
This study was supported by the:
  • Wellcome Trust (Award 204809/Z/16/Z)
    • Principle Award Recipient: BlairL Strang
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2021-11-01
2024-04-26
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References

  1. Coyne CB, Lazear HM. zika virus - reigniting the TORCH. Nat Rev Microbiol 2016; 14:707–715 [View Article] [PubMed]
    [Google Scholar]
  2. Barnes RD, Fairweather DV, Holliday J, Keane C, Piesowicz A et al. A germfree infant. Lancet 1969; 1:168–171 [View Article] [PubMed]
    [Google Scholar]
  3. Perez-Muñoz ME, Arrieta M-C, Ramer-Tait AE, Walter J. A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome. Microbiome 2017; 5:48 [View Article] [PubMed]
    [Google Scholar]
  4. Antony KM, Ma J, Mitchell KB, Racusin DA, Versalovic J et al. The preterm placental microbiome varies in association with excess maternal gestational weight gain. Am J Obstet Gynecol 2015; 212:653 [View Article] [PubMed]
    [Google Scholar]
  5. Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J et al. The placenta harbors a unique microbiome. Sci Transl Med 2014; 6:237ra65 [View Article] [PubMed]
    [Google Scholar]
  6. Prince AL, Ma J, Kannan PS, Alvarez M, Gisslen T et al. The placental membrane microbiome is altered among subjects with spontaneous preterm birth with and without chorioamnionitis. Am J Obstet Gynecol 2016; 214:627 [View Article] [PubMed]
    [Google Scholar]
  7. Collado MC, Rautava S, Aakko J, Isolauri E, Salminen S. Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. Sci Rep 2016; 6:23129 [View Article] [PubMed]
    [Google Scholar]
  8. Gomez-Arango LF, Barrett HL, McIntyre HD, Callaway LK, Morrison M et al. Contributions of the maternal oral and gut microbiome to placental microbial colonization in overweight and obese pregnant women. Sci Rep 2017; 7:2860 [View Article] [PubMed]
    [Google Scholar]
  9. Tomlinson MS, Bommarito PA, Martin EM, Smeester L, Fichorova RN et al. Microorganisms in the human placenta are associated with altered CPG methylation of immune and inflammation-related genes. PLoS One 2017; 12:e0188664 [View Article] [PubMed]
    [Google Scholar]
  10. Zheng J, Xiao X, Zhang Q, Mao L, Yu M et al. The placental microbiota is altered among subjects with gestational diabetes mellitus: A pilot study. Front Physiol 2017; 8:675 [View Article] [PubMed]
    [Google Scholar]
  11. Fischer LA, Demerath E, Bittner-Eddy P, Costalonga M. Placental colonization with periodontal pathogens: The potential missing link. Am J Obstet Gynecol 2019; 221:383–392 [View Article] [PubMed]
    [Google Scholar]
  12. Onderdonk AB, Delaney ML, DuBois AM, Allred EN, Leviton A et al. Detection of bacteria in placental tissues obtained from extremely low gestational age neonates. Am J Obstet Gynecol 2008; 198:110 [View Article]
    [Google Scholar]
  13. Martinez KA 2nd, Romano-Keeler J, Zackular JP, Moore DJ, Brucker RM et al. Bacterial dna is present in the fetal intestine and overlaps with that in the placenta in mice. PLoS One 2018; 13:e0197439 [View Article] [PubMed]
    [Google Scholar]
  14. Kliman HJ. Comment on "the placenta harbors a unique microbiome. Sci Transl Med 2014; 6:254254le4 [View Article]
    [Google Scholar]
  15. Aagaard KM. Author response to comment on “the placenta harbors a unique microbiome”. Sci Transl Med 2014; 6:254lr3 [View Article]
    [Google Scholar]
  16. Bushman FD. De-discovery of the placenta microbiome. Am J Obstet Gynecol 2019; 220:213–214 [View Article] [PubMed]
    [Google Scholar]
  17. Leiby JS, McCormick K, Sherrill-Mix S, Clarke EL, Kessler LR et al. Lack of detection of a human placenta microbiome in samples from preterm and term deliveries. Microbiome 2018; 6:196 [View Article] [PubMed]
    [Google Scholar]
  18. Lauder AP, Roche AM, Sherrill-Mix S, Bailey A, Laughlin AL et al. Comparison of placenta samples with contamination controls does not provide evidence for a distinct placenta microbiota. Microbiome 2016; 4:29 [View Article] [PubMed]
    [Google Scholar]
  19. Theis KR, Romero R, Winters AD, Greenberg JM, Gomez-Lopez N et al. Does the human placenta delivered at term have a microbiota? Results of cultivation, quantitative real-time PCR, 16S rrna gene sequencing, and metagenomics. Am J Obstet Gynecol 2019; 220:267 [View Article] [PubMed]
    [Google Scholar]
  20. Salter SJ, Cox MJ, Turek EM, Calus ST, Cookson WO et al. Reagent and laboratory contamination can critically impact sequence-based microbiome analyses. BMC Biol 2014; 12:87 [View Article] [PubMed]
    [Google Scholar]
  21. Lim ES, Rodriguez C, Holtz LR. Amniotic fluid from healthy term pregnancies does not harbor a detectable microbial community. Microbiome 2018; 6:87 [View Article] [PubMed]
    [Google Scholar]
  22. de Goffau MC, Lager S, Sovio U, Gaccioli F, Cook E et al. Human placenta has no microbiome but can contain potential pathogens. Nature 2019; 572:329–334 [View Article] [PubMed]
    [Google Scholar]
  23. Britt WJ. Maternal immunity and the natural history of congenital human cytomegalovirus infection. Viruses 2018; 10: [View Article] [PubMed]
    [Google Scholar]
  24. Njue A, Coyne C, Margulis AV, Wang D, Marks MA et al. The role of congenital cytomegalovirus infection in adverse birth outcomes: A review of the potential mechanisms. Viruses 2020; 13: [View Article] [PubMed]
    [Google Scholar]
  25. McDonagh S, Maidji E, Ma W, Chang H-T, Fisher S et al. Viral and bacterial pathogens at the maternal-fetal interface. J Infect Dis 2004; 190:826–834 [View Article] [PubMed]
    [Google Scholar]
  26. Gaccioli F, Lager S, de Goffau MC, Sovio U, Dopierala J et al. Fetal inheritance of chromosomally integrated human Herpesvirus 6 predisposes the mother to pre-eclampsia. Nat Microbiol 2020; 5:901–908 [View Article] [PubMed]
    [Google Scholar]
  27. Caserta MT, Hall CB, Schnabel K, Lofthus G, McDermott MP. Human Herpesvirus (HHV)-6 and HHV-7 infections in pregnant women. J Infect Dis 2007; 196:1296–1303 [View Article] [PubMed]
    [Google Scholar]
  28. Hall CB, Caserta MT, Schnabel KC, Shelley LM, Carnahan JA et al. Transplacental congenital human Herpesvirus 6 infection caused by maternal chromosomally integrated virus. J Infect Dis 2010; 201:505–507 [View Article] [PubMed]
    [Google Scholar]
  29. Ando Y, Kakimoto K, Ekuni Y, Ichijo M. HHV-6 infection during pregnancy and spontaneous abortion. Lancet 1992; 340:1289 [View Article] [PubMed]
    [Google Scholar]
  30. Revest M, Minjolle S, Veyer D, Lagathu G, Michelet C et al. Detection of HHV-6 in over a thousand samples: New types of infection revealed by an analysis of positive results. J Clin Virol 2011; 51:20–24 [View Article] [PubMed]
    [Google Scholar]
  31. Drago F, Broccolo F, Javor S, Drago F, Rebora A et al. evidence of human herpesvirus-6 and -7 reactivation in miscarrying women with pityriasis rosea. J Am Acad Dermatol 2014; 71:198–199 [View Article] [PubMed]
    [Google Scholar]
  32. Das BB, Rakheja D, Lacelle C, Sedlak RH, Gulve N et al. Possible progesterone-induced gestational activation of chromosomally integrated human Herpesvirus 6B and transplacental transmission of activated human herpesvirus 6B. J Heart Lung Transplant 2016; 35:1373–1376 [View Article] [PubMed]
    [Google Scholar]
  33. Avanzi S, Leoni V, Rotola A, Alviano F, Solimando L et al. Susceptibility of human placenta derived mesenchymal stromal/stem cells to human herpesviruses infection. PLoS One 2013; 8:e71412 [View Article] [PubMed]
    [Google Scholar]
  34. Koi H, Zhang J, Parry S. The mechanisms of placental viral infection. Annals of the New York Academy of Sciences 2001; 943:148–56 [View Article]
    [Google Scholar]
  35. Arechavaleta-Velasco F, Ma Y, Zhang J, McGrath CM, Parry S. Adeno-associated Virus-2 (AAV-2) causes trophoblast dysfunction, and placental AAV-2 infection is associated with preeclampsia. Am J Pathol 2006; 168:1951–1959 [View Article]
    [Google Scholar]
  36. Hermonat PL, Kechelava S, Lowery CL, Korourian S. Trophoblasts are the preferential target for human papilloma virus infection in spontaneously aborted products of conception. Human pathology 1998; 29:170–4
    [Google Scholar]
  37. Tanaka K, Chowdhury K, Chang KS, Israel M, Ito Y. Isolation and characterization of polyoma virus mutants which grow in murine embryonal carcinoma and trophoblast cells. EMBO J 1982; 1:1521–1527 [View Article]
    [Google Scholar]
  38. Human Microbiome Project Consortium The Integrative Human Microbiome Project: dynamic analysis of microbiome-host omics profiles during periods of human health and disease. Cell Host & Microbe 2014; 16:276–89 [View Article] [PubMed]
    [Google Scholar]
  39. Gevers D, Knight R, Petrosino JF, Huang K, McGuire AL et al. The Human Microbiome Project: a community resource for the healthy human microbiome. PLoS Biol 2012; 10:e1001377 [View Article] [PubMed]
    [Google Scholar]
  40. Human Microbiome Project C A framework for human microbiome research. Nature 2012; 486:215–221
    [Google Scholar]
  41. Li F, Chen C, Wei W, Wang Z, Dai J et al. The metagenome of the female upper reproductive tract. Gigascience 2018; 7:10 [View Article] [PubMed]
    [Google Scholar]
  42. Bolger AM, Lohse M, Usadel B. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics 2014; 30:2114–2120 [View Article] [PubMed]
    [Google Scholar]
  43. Wood DE, Salzberg SL. Kraken: Ultrafast metagenomic sequence classification using exact alignments. Genome Biol 2014; 15:R46 [View Article] [PubMed]
    [Google Scholar]
  44. Walker MA, Pedamallu CS, Ojesina AI, Bullman S, Sharpe T et al. GATK Pathseq: A customizable computational tool for the discovery and identification of microbial sequences in libraries from eukaryotic hosts. Bioinformatics 2018; 34:4287–4289 [View Article] [PubMed]
    [Google Scholar]
  45. Wickham H, Averick M, Bryan J, Chang W, McGowan L et al. Welcome to the tidyverse. JOSS 2019; 4:1686 [View Article]
    [Google Scholar]
  46. Nooij S, Schmitz D, Vennema H, Kroneman A, Koopmans MPG. Overview of virus metagenomic classification methods and their biological applications. Front Microbiol 2018; 9:749 [View Article] [PubMed]
    [Google Scholar]
  47. Li Z, Breitwieser FP, Lu J, Jun AS, Asnaghi L et al. Identifying corneal infections in formalin-fixed specimens using Next Generation sequencing. Invest Ophthalmol Vis Sci 2018; 59:280–288 [View Article] [PubMed]
    [Google Scholar]
  48. Barrientos-Somarribas M, Messina DN, Pou C, Lysholm F, Bjerkner A et al. Discovering viral genomes in human metagenomic data by predicting unknown protein families. Sci Rep 2018; 8:28 [View Article] [PubMed]
    [Google Scholar]
  49. Tyschik EA, Shcherbakova SM, Ibragimov RR, Rebrikov DV. Transplacental transmission of Torque Teno virus. Virol J 2017; 14:92 [View Article] [PubMed]
    [Google Scholar]
  50. Wylie KM, Mihindukulasuriya KA, Zhou Y, Sodergren E, Storch GA et al. Metagenomic analysis of double-stranded DNA viruses in healthy adults. BMC Biol 2014; 12:71 [View Article] [PubMed]
    [Google Scholar]
  51. Forslund O, Johansson H, Madsen KG, Kofoed K. The nasal mucosa contains a large spectrum of human papillomavirus types from the betapapillomavirus and gammapapillomavirus genera. J Infect Dis 2013; 208:1335–1341 [View Article] [PubMed]
    [Google Scholar]
  52. Sebghati M, Khalil A. New evidence on prognostic features, prevention and treatment of congenital cytomegalovirus infection. Curr Opin Obstet Gynecol 2020; 32:342–350 [View Article] [PubMed]
    [Google Scholar]
  53. Mocarski ES, Shenk T, Griffiths PD, Pass RF. Cytomegaloviruses. Knipe D, Howley P. eds In Fields Virology, 6th. edn New York, NY: Lippincott, Williams & Wilkins; 2015 pp 1960–2015
    [Google Scholar]
  54. Di Stefano M, Calabrò ML, Di Gangi IM, Cantatore S, Barbierato M et al. In vitro and in vivo human herpesvirus 8 infection of placenta. PLoS One 2008; 3:e4073 [View Article] [PubMed]
    [Google Scholar]
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