Edited by Jeffrey I. Gordon, Washington University School of Medicine in St. Louis, St. Louis, MO, and approved July 17, 2015 (received for review February 11, 2015)
The human indigenous microbial communities (microbiota) play critical roles in health and may be especially important for mother and fetus during pregnancy. Using a case-control cohort of 40 women, we characterized weekly variation in the vaginal, gut, and oral microbiota during and after pregnancy. Microbiota membership remained relatively stable at each body site during pregnancy. An altered vaginal microbial community was associated with preterm birth; this finding was corroborated by an analysis of samples from an additional cohort of nine women. We also discovered an abrupt change in the vaginal microbiota at delivery that persisted in some cases for at least 1 y. Our findings suggest that pregnancy outcomes might be predicted by features of the microbiota early in gestation.
Despite the critical role of the human microbiota in health, our understanding of microbiota compositional dynamics during and after pregnancy is incomplete. We conducted a case-control study of 49 pregnant women, 15 of whom delivered preterm. From 40 of these women, we analyzed bacterial taxonomic composition of 3,767 specimens collected prospectively and weekly during gestation and monthly after delivery from the vagina, distal gut, saliva, and tooth/gum. Linear mixed-effects modeling, medoid-based clustering, and Markov chain modeling were used to analyze community temporal trends, community structure, and vaginal community state transitions. Microbiota community taxonomic composition and diversity remained remarkably stable at all four body sites during pregnancy (P > 0.05 for trends over time). Prevalence of a Lactobacillus-poor vaginal community state type (CST 4) was inversely correlated with gestational age at delivery (P = 0.0039). Risk for preterm birth was more pronounced for subjects with CST 4 accompanied by elevated Gardnerella or Ureaplasma abundances. This finding was validated with a set of 246 vaginal specimens from nine women (four of whom delivered preterm). Most women experienced a postdelivery disturbance in the vaginal community characterized by a decrease in Lactobacillus species and an increase in diverse anaerobes such as Peptoniphilus, Prevotella, and Anaerococcus species. This disturbance was unrelated to gestational age at delivery and persisted for up to 1 y. These findings have important implications for predicting premature labor, a major global health problem, and for understanding the potential impact of a persistent, altered postpartum microbiota on maternal health, including outcomes of pregnancies following short interpregnancy intervals.
↵1D.B.D. and B.J.C. contributed equally to this work.
Author contributions: D.B.D., D.J.L., G.S., D.K.S., S.P.H., and D.A.R. designed research; D.B.D., A.R., and R.J.W. performed research; B.J.C., P.J.M., and S.P.H. contributed new reagents/analytic tools; D.B.D., B.J.C., P.J.M., E.K.C., C.L.S., D.S.A.G., S.P.H., and D.A.R. analyzed data; and D.B.D., B.J.C., P.J.M., E.K.C., C.L.S., D.S.A.G., S.P.H., and D.A.R. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: Raw sequence data have been deposited at the Sequence Read Archive (SRP no. 288562).
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1502875112/-/DCSupplemental.
Freely available online through the PNAS open access option.
