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8: Whole metagenomic shotgun sequencing reveals a vibrant placental microbiome harboring metabolic function

      Objective

      Humans and our microbiota have co-evolved as a metabolic and antigenic commune (“microbiome”) with a collective genome (“metagenome”) which retains body site-specific niches. To date, the human placental microbiome has yet to be robustly interrogated. Since the placenta harbors diverse metabolic and immune regulatory functions, it is unlikely to be “sterile” and is likely a uniqe microbiome niche. Our aim was to leverage our developed Human Microbiome Project pipelines to identify community membership (placental microbiome) and function (metagenomic carriage of metabolic pathways).

      Study Design

      In a strictly matched-cohort design, placentas (n 12) were rigorously sterile collected from term gravidae and stratified by presence or absence of remote antenatal infection (e.g., uncomplicated UTI). Genomic DNA was extracted (MoBIO), and metagenomic libraries were subjected to shotgun sequencing (WGS; Illumina). Host (human) DNA was filter binned, and microbial DNA was analyzed with MG_RAST (taxonomic abundance) and HuMAaN (metabolic pathway reconstruction).

      Results

      >200 million reads (>36 gigabytes) of WGS data were generated, and 357 megabytes of binned microbial data was analyzed. In total, the placental microbiome comprised of 728 species (from among 329 genus). From the 65 most abundant genus, robust metabolic reconstruction revealed 2413 encoded prokaryotic genes. Antental infection signficatnly increased abundance, diversity, and richness of genus (LDA effect size>4, A), resulting in distinct functional metabolic pathways (B,C). The placental microbiome was not significantly structured by maternal BMI> 30 nor mode of delivery.

      Conclusion

      Metagenomic sequencing reveals for the first time that there exists a vibrant and functional placental microbiome community which is structured by a remote history of maternal antenatal infection. We speculate that the placental microbiome likely contributes to both its metabolic and immune functions, and is essential to human reproduction.
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      Metagenomics of the human placental microbiome