The vaginal microenvironment prior to incident STI
RM Brotman1, JL Borgogna2, CK Robinson1, MA Klebanoff3, CJ Yeoman2, J Ravel1, MD Shardell4 1Institute for Genome Sciences, University of Maryland; 2Montana State University; 3Ohio State University; 4National Institute on Aging
We conducted a nested case control study in the NIH's Longitudinal Study of Vaginal Flora (LSVF) to assess the vaginal microenvironment of 397 cases at the visit prior to an incident genital STI (Chlamydia trachomatis, Neisseria gonorrhea, or Trichomonas vaginalis) compared to 1,794 STI-negative controls. Vaginal microbiota, metabolites, and lactic acid isomers were assessed for factors that were associated with incident STI. Controls were matched to cases on age, race and follow-up time. Vaginal lavages and behavioral surveys were collected every three months for one year. Microbiota composition was characterized and bacterial community state types (CSTs) were assigned by hierarchical clustering. Conditional logistic regression with covariate adjustment (partner concurrency, number of sex partners, condom use) was used for modeling. P-values were computed using 1000 matching group-stratified permutations and 95% confidence intervals using 1000 bootstrap samples clustered by matching group. Women with a CST IV-A profile, low-Lactobacillus states dominated by high relative abundance of BVAB-1 and low G. vaginalis, had the highest odds of incident STI. CST-I (L. crispatus-dominated), CST-II (L. gasseri-dominated), CST-III-A, and CST-III-C (both L iners dominated with the latter having other Lactobacillus spp.) each had more than 50% lower odds of incident STI than women in CST IV-A (all p<0.01). CST-II had the lowest point estimate with a 72% reduction in the odds of STI outcome (p=.02). High concentration of the D-isomer of lactic acid was associated with lower STI risk, irrespective of L-isomer concentration (p<0.05). Combinations of D- and L-isomers of lactic acid that were associated with low STI risk included a disproportionately large number of participants in CST-I and CST III-A (p<0.01). Metabolomic analysis indicated multiple amino acids and higher concentrations of several biogenic amines were associated with higher STI risk (q-value<0.05). Microbial and chemical composition of the vaginal microenvironment may modulate STI risk. Metagenomic and immunologic data are currently being integrated into multi-omics models with pathogen-specific outcomes.
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