Microbiome And Multi'Omics In Preterm Birth: The Bacteria And Birth Study

Specific Aim 1. Longitudinal maternal (vaginal, oral, skin, gut), fetal (oral, skin, gut) and placental (basal plate and parenchyma) 16S-based metagenomic profiling with inferred metagenomics will reveal distinct microbial communities in association with preterm birth. Methods: We will enroll 526 at-risk gravidae to yield an approximated 135 preterm births with 401 at-risk term controls. Starting in the first/early second trimester, we will sample multiple body sites (vagina, oral, stool, placenta) at multiple time points (antenatal through delivery), isolate microbial DNA, and perform 16S-based determination of niche-specific microbial communities found in association with preterm birth. With our case-cohort longitudinal design, we will be able to apply our well-developed supervised learning approaches to reveal which taxa contribute to risk of preterm birth, and at what body sites and gestational ages they are predictive of preterm birth. Specific Aim 2. Whole-genome shotgun (WGS) metagenomics from selected subjects and body sites will enable species identification, generation of microbial gene catalogues, and metabolic reconstructions to determine the structure, function and diversity of the preterm birth microbiome. Methods: To probe metabolic functionality and describe pathogen-related mechanisms, we will analyze changes in total gene content using shotgun metagenomics on a subset of samples. We will build on our functional computational pipelines to fully characterize targeted subjects' metagenomic signatures. Specific Aim 3. Integrated host genomics, metatranscriptomics and metabonomics data will reveal molecular mechanisms and networks underlying preterm birth in a limited subset of samples. Methods: We will interrogate and integrate our concomitantly acquired clinical metadata, microbial and host gene expression data (RNA-Seq metatranscriptomics), and metabonomics profiling with advanced computational and biostatistical approaches. We will be guided in our choice of subjects by our data from Aims 1 and 2.