Placental Microbiome: a Paradigm Shift or Flaw in the Methodology?

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Abstract

Rapid development of high-throughput DNA sequencing technologies and bioinformatics methods, together with a substantial reduction of their cost, have provided tremendous opportunities for studying the human microbiome. In recent years, much attention has been paid to studies of the microbiome of the upper reproductive tract of woman and the fetoplacental system, which have traditionally been considered sterile. Obtaining irrefutable evidence of the existence of the placental microbiome would enable us to believe with a high degree of certainty that microorganisms colonize the fetus already in the womb, which would have far-reaching consequences not only for medicine, but also for basic biology. This issue triggered a heated discussion among microbiologists, molecular biologists, obstetricians, and neonatologists. In the past few years, a number of studies have been published, both refuting and confirming the dogma, accepted for many decades, that the placenta and fetus are sterile during a healthy pregnancy. This literature review is a critical analysis of the results of studies into the placental microbiome. It provides arguments both for supporters of the hypothesis of the resident microbiota of the placenta and their opponents. Particular attention is paid to the methodological requirements for molecular studies of biological material with low microbial biomass, compliance with which is crucial for obtaining reliable results.

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Elena V. Shipitsyna

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology

Author for correspondence.
Email: shipitsyna@inbox.ru
ORCID iD: 0000-0002-2309-3604
SPIN-code: 7660-7068
Scopus Author ID: 14071984800
ResearcherId: K-1271-2018

PhD in Biology

Russian Federation, 3 Mendeleevskaya Line, 199034, St. Petersburg, Russia

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Supplementary files

Supplementary Files
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1. Fig. 1. Schematic representation of two opposing concepts of the formation of the primary human microbiota: A - the placenta and the fetus are sterile during a healthy pregnancy, and the intestinal microbiota of the child is formed during and after childbirth, while in the case of vaginal delivery, the microbiota of the newborn is similar to the microbiota of the mother's vagina, in the case of Caesarean section - with the microbiota of her skin; B - the microbiota of the fetus is formed in the womb, and its source is the microbiota of the placenta, which, in turn, comes from bacteria in the intestines or the mouth of the mother. Adapted from: M. Perez-Muñoz et al. [19].

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2. Fig 2. The number of copies of the 16S rRNA gene, determined by quantitative PCR in the analysis of samples of placenta, saliva, vagina (obtained from 6 women) and negative controls. Adapted from: A. Lauder et al. [12]

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3. Fig 3. Bacterial composition of samples of placenta, saliva and negative controls,% of the total content of bacteria. DNA was isolated using a set of reagents MO BIO (A), PSP (B). The microbial composition of the placenta samples resembles the composition of the negative control samples, while the microbiota is detected in the saliva, the composition of which does not depend on the DNA extraction kit Adapted from: D. Kim et al. [47].

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