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

Abstract

The existence of a placental microbiota is debated. The human placenta has historically been considered sterile and microbial colonization was associated with adverse pregnancy outcomes. Yet, recent DNA sequencing investigations reported a microbiota in typical human term placentas. However, this detected microbiota could represent background DNA or delivery-associated contamination. Using fifteen publicly available 16S rRNA gene datasets, existing data were uniformly re-analyzed with DADA2 to maximize comparability. While Amplicon Sequence Variants (ASVs) identified as Lactobacillus, a typical vaginal bacterium, were highly abundant and prevalent across studies, this prevalence disappeared after applying likely DNA contaminant removal to placentas from term cesarean deliveries. A six-study sub-analysis targeting the 16S rRNA gene V4 hypervariable region demonstrated that bacterial profiles of placental samples and technical controls share principal bacterial ASVs and that placental samples clustered primarily by study origin and mode of delivery. Contemporary DNA-based evidence does not support the existence of a placental microbiota.ImportanceEarly-gestational microbial influences on human development are unclear. By applying DNA sequencing technologies to placental tissue, bacterial DNA signals were observed, leading some to conclude that a live bacterial placental microbiome exists in typical term pregnancy. However, the low-biomass nature of the proposed microbiome and high sensitivity of current DNA sequencing technologies indicate that the signal may alternatively derive from environmental or delivery-associated bacterial DNA contamination. Here we address these alternatives with a re-analysis of 16S rRNA gene sequencing data from 15 publicly available placental datasets. After identical DADA2 pipeline processing of the raw data, subanalyses were performed to control for mode of delivery and environmental DNA contamination. Both environment and mode of delivery profoundly influenced the bacterial DNA signal from term-delivered placentas. Aside from these contamination-associated signals, consistency was lacking across studies. Thus, placentas delivered at term are unlikely to be the original source of observed bacterial DNA signals.

From Birth to Weaning: A Window of Opportunity for Microbiota

“…Historically, the placenta was considered a sterile organ, but, in recent years, new evidence has demonstrated the possible existence of a placental microbiome. In 2014, the first studies based on bacterial DNA demonstrated the existence of a placental microbiota even during full-term and normal pregnancies [ 24 ].…”

Reducing the Risk of Pre-Eclampsia in Women with Polycystic Ovary Syndrome Using a Combination of Pregnancy Screening, Lifestyle, and Medical Management Strategies

“…Lv et al observed an expansion in the relative abundance of periodontal disease-associated bacteria, such as Fusobacterium , and a decrease in the abundance of SCFA-producing bacteria, such as Faecalibacterium and Akkermansia , in the gut microbiome of women with early-onset PE [ 225 ]. There is ongoing debate regarding the existence and role of a placenta-specific microbiome [ 226 ].…”

Between Dysbiosis, Maternal Immune Activation and Autism: Is There a Common Pathway?

“…However, this statement has recently been reassessed by a limited number of studies confirming the presence of microorganisms in the placenta [ 24 , 25 , 26 ]. These results are still the subject of debate in the scientific community, and there is no clear conclusion [ 27 ].…”