No evidence for a placental microbiome in human pregnancies at term

Abstract

BACKGROUND: The placenta plays an important role in the modulation of pregnancy immunity; however, there is no consensus regarding the existence of a placental microbiome in healthy full-term pregnancies. OBJECTIVE: This study aimed to investigate the existence and origin of a placental microbiome. STUDY DESIGN: A cross-sectional study comparing samples (3 layers of placental tissue, amniotic fluid, vernix caseosa, and saliva, vaginal, and rectal samples) from 2 groups of full-term births: 50 women not in labor with elective cesarean deliveries and 26 with vaginal deliveries. The comparisons were performed using polymerase chain reaction amplification and DNA sequencing techniques and bacterial culture experiments. RESULTS: There were no significant differences regarding background characteristics between women who delivered by elective cesarean and those who delivered vaginally. Quantitative measurements of bacterial content in all 3 placental layers (quantitative polymerase chain reaction of the 16S ribosomal RNA gene) did not show any significant difference among any of the sample types and the negative controls. Here, 16S ribosomal RNA gene sequencing of the maternal side of the placenta could not differentiate between bacteria in the placental tissue and contamination of the laboratory reagents with bacterial DNA. Probe-specific quantitative polymerase chain reaction for bacterial taxa suspected to be present in the placenta could not detect any statistically significant difference between the 2 groups. In bacterial cultures, substantially more bacteria were observed in the placenta layers from vaginal deliveries than those from cesarean deliveries. In addition, 16S ribosomal RNA gene sequencing of bacterial colonies revealed that most of the bacteria that grew on the plates were genera typically found in human skin; moreover, it revealed that placentas delivered vaginally contained a high prevalence of common vaginal bacteria. Bacterial growth inhibition experiments indicated that placental tissue may facilitate the inhibition of bacterial growth. CONCLUSION: We found no evidence to support the existence of a placental microbiome in our study of 76 term pregnancies, which used polymerase chain reaction amplification and sequencing techniques and bacterial culture experiments. Incidental findings of bacterial species could be due to contamination or to low-grade bacterial presence in some locations; such bacteria do not represent a placental microbiome per se.

Maternal-Fetal Immune Responses in Pregnant Women Infected with SARS-CoV-2

“…Traditionally, the placenta is considered a sterile organ 107,108 . Indeed, recent research has reiterated the sterile womb hypothesis using placentas from women who delivered via cesarean section at term without labor [109][110][111] as well as studies in mice 112,113 and non-human primates 114 .…”

“…Traditionally, the placenta is considered a sterile organ 107 , 108 . Indeed, recent research has reiterated the sterile womb hypothesis using placentas from women who delivered via cesarean section at term without labor 109 – 111 as well as studies in mice 112 , 113 and non-human primates 114 . Here, we evaluated the possibility that maternal SARS-CoV-2 infection compromises the sterility of the placenta by facilitating the invasion of bacteria or the transfer of bacterial DNA from maternal compartments.…”

Group therapy on in utero colonization: seeking common truths and a way forward

“…Overall, studies using 16S rRNA gene amplicon sequencing support the idea that the noise is too high to draw consistent conclusions about a ‘microbiome’ in the villous placenta. Research supporting the sterile womb hypothesis posits that data suggesting the presence of microbial communities in the placenta are actually due to contamination of placental samples during delivery or during the processing of bacterial DNA [ 15 , 16 ]. For example, using 16S rRNA sequencing, De Goffau and colleagues identified several sources of contamination, including labor and delivery and sample processing that are associated with different bacterial signals and concluded that they find no clear evidence of a placental microbiome.…”

“…They identified some samples with low biomass bacterial signal, but concluded that the source of this signal was due to contamination. Similarly, Sterpu et al found no significant differences between placental samples and controls based on 16S data, with the majority of their samples being flagged as contaminants by decontamination software [ 16 ]. However, they found that the median gene counts for bacterial signal were highest for the maternal side of the placenta regardless of the mode of delivery and indeed detected sporadic bacteria.…”

The reproductive tract microbiota in pregnancy

“…If a unique microbiome existed in the placenta an immunologically naïve foetus could be overwhelmed [ 51 ]. Therefore, there may be bacteria present at a low level in the placenta but given the function of the placenta, normal bacterial colonisation and development of a placental niche seems unlikely [ 59 ].…”