Host factors are associated with vaginal microbiome structure in pregnancy in the ECHO Cohort Consortium

Abstract

Using pooled vaginal microbiota data from pregnancy cohorts (N = 683 participants) in the Environmental influences on Child Health Outcomes (ECHO) Program, we analyzed 16S rRNA gene amplicon sequences to identify clinical and demographic host factors that associate with vaginal microbiota structure in pregnancy both within and across diverse cohorts. Using PERMANOVA models, we assessed factors associated with vaginal community structure in pregnancy, examined whether host factors were conserved across populations, and tested the independent and combined effects of host factors on vaginal community state types (CSTs) using multinomial logistic regression models. Demographic and social factors explained a larger amount of variation in the vaginal microbiome in pregnancy than clinical factors. After adjustment, lower education, rather than self-identified race, remained a robust predictor of L. iners dominant (CST III) and diverse (CST IV) (OR = 8.44, 95% CI = 4.06-17.6 and OR = 4.18, 95% CI = 1.88-9.26, respectively). In random forest models, we identified specific taxonomic features of host factors, particularly urogenital pathogens associated with pregnancy complications (Aerococcus christensenii and Gardnerella spp.) among other facultative anaerobes and key markers of community instability (L. iners). Sociodemographic factors were robustly associated with vaginal microbiota structure in pregnancy and should be considered as sources of variation in human microbiome studies.

Keywords: 16S rRNA gene amplicon sequence data; ECHO cohort; Host factors; Meta-analysis; Pregnancy; Vaginal microbiota structure.

Figure 1

(a) Principal coordinates (PCoA) analysis of Bray–Curtis distances between samples based on amplicon sequence variants (ASVs) and (b) phylotypes demonstrating that using phylogenetic placement of ASVs on a reference tree removed a large degree of variation by site.

Figure 2

Community state types (CSTs) by ECHO cohort. CST I, Lactobacillus crispatus dominant; CST II, L. gasseri dominant; CST III, L. iners dominant; CST IV-B, diverse, characterized by high relative abundance of Gardnerella spp., low relative abundance of Candidatus Lachnocurva vaginae (formerly known as BVAB1), and moderate relative abundance of Fannyhessea vaginae (previously Atopobium vaginae); CST IV-C, diverse array of facultative and strictly anaerobic bacteria, with low relative abundance of Lactobacillus spp., G. vaginalis, Fannyhessea vaginae, and Ca. L. vaginae); CST V, L. jenseni dominant.

Figure 3

Single-adjusted (left) and multifactor-adjusted (left) permutational multivariate analysis of variance (PERMANOVA) pooled estimates of vaginal microbiota structure in pregnancy using Bray–Curtis distances across all cohorts. Only factors that were significantly associated with composition (p < 0.05) in single-factor models were retained for inclusion in the multifactor model using backward selection. FDR false discovery rate.

Figure 4

Associations between vaginal microbiota community structure and host factors across cohorts. Single-adjusted (left) and multifactor-adjusted (left) PERMANOVA estimates of vaginal microbiota structure in pregnancy using Bray–Curtis distances by individual cohort. Only factors that were significantly associated with composition (p < 0.05) in single-factor models were retained for inclusion in the multifactor model using backward selection.

Figure 5

Random forest panel plots of the top ranked vaginal taxonomic features predictive of host factors.