Longitudinal dynamics of the human vaginal ecosystem across the reproductive cycle

Costello, E. K.; DiGiulio, D. B.; Robaczewska, A.; Symul, L.; Wong, R. J.; Shaw, G. M.; Stevenson, D. K.; Holmes, S. P.; Kwon, D. S.; Relman, D. A.

doi:10.1101/2022.11.20.517263

bioRxiv · 10.1101/2022.11.20.517263

Longitudinal dynamics of the human vaginal ecosystem across the reproductive cycle

Costello, E. K.·DiGiulio, D. B.·Robaczewska, A.·Symul, L.·Wong, R. J.·Shaw, G. M.·Stevenson, D. K.·Holmes, S. P.·Kwon, D. S.·Relman, D. A.

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Abstract

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.

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Costello, E. K., DiGiulio, D. B., Robaczewska, A., Symul, L., Wong, R. J., Shaw, G. M., Stevenson, D. K., Holmes, S. P., Kwon, D. S., Relman, D. A.. 2022-11-21. Longitudinal dynamics of the human vaginal ecosystem across the reproductive cycle. https://doi.org/10.1101/2022.11.20.517263

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