Bacterial profiles of the human placenta from term and preterm deliveries

Abstract

Whether the human placenta is a sterile organ is under debate. Yet, infection of the amniotic cavity, including the placenta, is causally linked to preterm birth. This study compares the bacterial profiles of term and preterm placentas through culture and 16S rRNA gene sequencing of the amnion, amnion-chorion interface, subchorion, villous tree, and basal plate, while accounting for patient identity, mode of delivery, presence/absence of labor, and potential background DNA contamination. As no evidence of a placental microbiota in term pregnancy was found, these placentas were considered as controls. Placentas from preterm birth cases were more likely to yield bacterial cultures, and their bacterial DNA profiles were less rich than those of term controls, suggesting the predominance of only a few bacteria. Nevertheless, the bacterial DNA profiles of placentas from preterm cases and term controls were not consistently different. The placentas from preterm cases may often have a microbiota but the bacteria constituting these communities varied among the women. Mode of delivery had a pronounced effect on the bacterial profiles of all sampled levels of the placenta. Specifically, the bacterial DNA profiles of vaginally delivered placentas had higher relative abundances of Finegoldia, Gardnerella, Peptoniphilus, and Prevotella (each a common resident of the vaginal microbiota) than the profiles of cesarean-delivered placentas. Collectively, these data indicate that there is a not a placental microbiota in normal term pregnancy, and that although the placentas of some preterm cases were populated by bacteria, the identities of these bacteria varied among women delivering preterm.

Is there a placental microbiota? A critical review and re-analysis of published placental microbiota datasets

“…Fifteen studies (Table 1) were included in this re-analysis of investigations of the existence of a placental microbiota. Seven included sequence data from the V4 hypervariable region of the 16S rRNA gene (29, 39, 41, 43, 44, 50, 86), allowing for direct comparisons of sequence data across six of those studies (29, 39, 41, 44, 50, 86); one study could not be included in the direct comparison due to short read lengths of sequences in the publicly available dataset (43). Three of the remaining studies included sequence data from the V1-V2 16S rRNA gene hypervariable region (36–38), two studies sequenced the V6-V8 region (40, 53), and one study each sequenced the V3-V4 (58), V4-V5 (57), and V5-V7 (42) regions.…”

“…Mode of delivery must be taken into account when investigating the existence and structure of a placental bacterial DNA signal Eleven studies (27,38,43,44,52,54,57,59) concluded that the bacterial DNA signals in placentas from cesarean deliveries were not significantly different from those in placentas delivered vaginally. Yet, six other studies (36,38,42,51,86,89) have reported that the bacterial DNA signals in placentas from vaginal and cesarean deliveries significantly differ. The latter studies have reported increased prevalence and relative abundance of Lactobacillus and other vaginally associated taxa in placentas from vaginal deliveries.…”

“…Lactobacillus ASVs were among the top five ranked ASVs in three (39,57,86) of the six datasets which could be restricted to placental samples from cesarean term deliveries (Table 2).…”

“…Finally, similar to the results presented here in this re-analysis, the prevalence of Lactobacillus across placental samples in prior studies has been acknowledged, yet so too has been the high variability in the bacterial taxa reported within placental tissues across studies. Indeed, variability is high even across studies of similar cohorts from the same research groups (27,41,44,(63)(64)(65)86). The current study sought to remedy the lack of consensus in the literature regarding the existence of a placental microbiota in typical term pregnancy through a re-analysis of the current publicly available data on placental microbiotas while controlling for targeted region of the 16S rRNA gene for sequencing, background DNA contamination, and mode of delivery.…”

“…Given these current conflicting conclusions regarding the existence of a placental microbiota, here we performed a critical review and re-analysis of fifteen publicly available 16S rRNA gene sequencing datasets from human placental microbiota studies for which sample distinguishing metadata were available (29, 36–44, 50, 53, 57, 86). In this re-analysis we standardized the analytical process to enable assessment of taxonomic consistency in placental bacterial profiles across studies conducted by different laboratories across the world (Figure S1) .…”