The placenta harbors a unique microbiome

Abstract

Humans and their microbiomes have coevolved as a physiologic community composed of distinct body site niches with metabolic and antigenic diversity. The placental microbiome has not been robustly interrogated, despite recent demonstrations of intracellular bacteria with diverse metabolic and immune regulatory functions. A population-based cohort of placental specimens collected under sterile conditions from 320 subjects with extensive clinical data was established for comparative 16S ribosomal DNA-based and whole-genome shotgun (WGS) metagenomic studies. Identified taxa and their gene carriage patterns were compared to other human body site niches, including the oral, skin, airway (nasal), vaginal, and gut microbiomes from nonpregnant controls. We characterized a unique placental microbiome niche, composed of nonpathogenic commensal microbiota from the Firmicutes, Tenericutes, Proteobacteria, Bacteroidetes, and Fusobacteria phyla. In aggregate, the placental microbiome profiles were most akin (Bray-Curtis dissimilarity <0.3) to the human oral microbiome. 16S-based operational taxonomic unit analyses revealed associations of the placental microbiome with a remote history of antenatal infection (permutational multivariate analysis of variance, P = 0.006), such as urinary tract infection in the first trimester, as well as with preterm birth <37 weeks (P = 0.001).

Conflict of interest statement

Competing interests: J.P. is the president and chief science officer of Metanome Inc. J.V. received unrestricted research support from Biogaia AB (Stockholm, Sweden). All other authors declare that they have no competing interests.

Copyright © 2014, American Association for the Advancement of Science.

Figures

Fig. 1. The placental microbiome has a taxonomic profile that is similar to the oral microbiome

Bray-Curtis (B–C) dissimilarity was calculated using WGS-generated phylum-level abundance of bacteria from each body site, including placental data from this study; gut, vagina, posterior auricular skin, and nasal airways data from the HMP; and vaginal data from previously published gravidae (–4). The thicker the connecting line, the greater the similarity of the taxonomic profile (Bray-Curtis

Fig. 2. Comparison of WGS-generated taxa and metabolic capacity among body sites reveals distinct features of the placental microbiome

(A) The phylum-level abundance (y axis) is represented by vertical bars indicating the dominant phylum for each of seven body sites, where each bar indicates an independent subject grouped by body site niche. The phylum-level abundance for specific taxa is relatively stable among all placental specimens when compared with that of the oral sites. (B) The bubble plot shows the prevalence and relative abundance of representative species at each body site, projected as a composite to scale. (C) The relative abundance of metabolic pathways generated by HUMAnN is similarly represented by subject (vertical bars), and demonstrates the functional profile variations of the placenta and vaginal posterior fornix as distinct from other body sites.

Fig. 3. The placental microbiome from pregnancies complicated by a preterm delivery demonstrates discrete taxonomic profiles and variations in metabolic pathways

(A) Jackknife-supported PCoA plot demonstrates the beta diversity of the placental microbiome community at the OTU level on weighted UniFrac distance from 16S-derived microbial sequences (PERMANOVA, P = 0.001). (B) Bacterial taxa derived from WGS sequence data identified as differentially abundant between placental specimens from preterm birth versus term gestations as analyzed by Boruta feature selection (box plots representing the first quartile, median, and third quartile). In (A) and (B), samples are labeled as preterm (red) and term delivery (gray). (C) Heat map demonstrating the MG-RAST–generated metabolic activity of the placental microbiome. Stronger intensity of blue indicates higher pathway activity. Pathways (rows) are hierarchically clustered on Manhattan distance. Samples (columns) were ordered on the basis of the gestational weeks.

Fig. 4. A remote history of maternal antenatal infection correlates with the placental microbiome community

(A) PCoA plot shows the beta diversity of the placental microbiome community at OTU level with unweighted UniFrac distance derived from 16S-based sequencing data (PERMANOVA, P = 0.006). The first principal coordinates of the placental community structure from individuals with or without UTI are shown in the panel. (B to D) WGS-derived bacterial taxa were identified as differentially abundant between gravidae with and without a history of remote antenatal infection as analyzed (B) by LEfSe and (C) by LEfSe projected as a cladogram and (D) analyzed by Boruta feature selection. (E) The relative abundance of WGS-derived KEGG functional pathways was determined by MG-RAST and compared by LEfSe. As shown, lipopolysaccharide biosynthesis pathways are represented to a greater degree in the placental specimens from women with a remote history of antenatal infection. In all panels, red bars and dots are used to designate cases with a remote history of antenatal infection, and gray to designate noninfected controls.