DiGiulio, D. B. | Search bioRxiv

bioRxiv2022

Longitudinal dynamics of the human vaginal ecosystem across the reproductive cycle

The vaginal ecosystem is closely tied to human health and reproductive outcomes. However, its dynamics in the wake of childbirth remain poorly characterized. Here, we profiled the vaginal microbiota and cytokine milieu of subjects sampled throughout pregnancy (two cohorts; n = 196 pregnancies) and, in a subset, for one year postpartum (one cohort; n = 72 pregnancies). Delivery was associated with a vaginal pro-inflammatory cytokine response and the depletion of dominant taxa - typically, Lactobacillus species. By contrast, neither the progression of gestation nor the approach of labor strongly altered the vaginal ecosystem. At ~9.5 months postpartum (the latest timepoint at which cytokines were analyzed), elevated inflammation was associated with vaginal bacterial communities that had remained perturbed (i.e., highly diverse) from the time of delivery. Using time-to-event analysis, we found that the one-year postpartum probability of transitioning to Lactobacillus dominance was 49.4% (95% confidence interval (CI) [33.6%, 61.5%]; n = 58 at-risk cases, 86.2% of whom experienced this state prior to delivery). As diversity and inflammation declined postpartum, dominance by L. crispatus, the quintessential health-associated state, failed to recover: its prevalence before, immediately after, and one year after delivery was 41%, 4%, and 9%, respectively. Over the same period, states quasi-dominated by non-Lactobacillus species grew more common. Prompted by these findings, we revisited our pre-delivery data, discovering that a history of prior live birth was associated with a lower odds of L. crispatus dominance in pregnant subjects (odds ratio (OR) 0.14; 95% CI [0.06, 0.32]; P < 0.001) - an outcome modestly tempered by a longer (>18-month) interpregnancy interval. Our results suggest that reproductive history and childbirth in particular remodel the vaginal ecosystem and that the timing and degree of recovery from delivery may help determine the subsequent health of the woman and of future pregnancies.

microbiology↗

bioRxiv2018

Metagenomic analysis with strain-level resolution reveals fine-scale variation in the human pregnancy microbiome

Recent studies suggest that the microbiome has an impact on gestational health and outcome. However, characterization of the pregnancy-associated microbiome has largely relied on 16S rRNA gene amplicon-based surveys. Here, we describe an assembly-driven, metagenomics-based, longitudinal study of the vaginal, gut, and oral microbiomes in 292 samples from ten subjects sampled every three weeks throughout pregnancy. 1.53 Gb of non-human sequence was assembled into scaffolds, and functional genes were predicted for gene-and pathway-based analyses. Vaginal assemblies were binned into 97 draft quality genomes. Redundancy analysis (RDA) of microbial community composition at all three body sites revealed gestational age to be a significant source of variation in patterns of gene abundance. In addition, health complications were associated with variation in community functional gene composition in the mouth and gut. The diversity of Lactobacillus iners-dominated communities in the vagina, unlike most other vaginal community types, significantly increased with gestational age. The genomes of co-occurring Gardnerella vaginalis strains with predicted distinct functions were recovered in samples from two subjects. In seven subjects, gut samples contained strains of the same Lactobacillus species that dominated the vaginal community of that same subject, and not other Lactobacillus species; however, these within-host strains were divergent. CRISPR spacer analysis suggested shared phage and plasmid populations across body sites and individuals. This work underscores the dynamic behavior of the microbiome during pregnancy and suggests the potential importance of understanding the sources of this behavior for fetal development and gestational outcome.

microbiology↗