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. 2016 Sep 9;11(9):e0162302.
doi: 10.1371/journal.pone.0162302. eCollection 2016.

Urinary Microbiota Associated With Preterm Birth: Results From the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) Study

Free PMC article

Urinary Microbiota Associated With Preterm Birth: Results From the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) Study

Nicholas J Ollberding et al. PLoS One. .
Free PMC article


Preterm birth (PTB) is the leading cause of infant morbidity and mortality. Genitourinary infection is implicated in the initiation of spontaneous PTB; however, examination of the urinary microbiota in relation to preterm delivery using next-generation sequencing technologies is lacking. In a case-control study nested within the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) study, we examined associations between the urinary microbiota and PTB. A total of 49 cases (delivery < 37 weeks gestation) and 48 controls (delivery ≥ 37 weeks gestation) balanced on health insurance type were included in the present analysis. Illumina sequencing of the 16S rRNA gene V4 region was performed on urine samples collected during the second trimester. We observed no difference in taxa richness, evenness, or community composition between cases and controls or for gestational age modeled as a continuous variable. Operational taxonomic units (OTUs) classified to Prevotella, Sutterella, L. iners, Blautia, Kocuria, Lachnospiraceae, and S.marcescens were enriched among cases (FDR corrected p≤ 0.05). A urinary microbiota clustering partition dominated by S. marcescens was also associated with PTB (OR = 3.97, 95% CI: 1.19-13.24). These data suggest a limited role for the urinary microbiota in PTB when measured during the second trimester by 16S rRNA gene sequencing. The enrichment among cases in several organisms previously reported to be associated with genitourinary pathology requires confirmation in future studies to rule out the potential for false positive findings.

Conflict of interest statement

The authors have declared that no competing interests exist.


Fig 1
Fig 1. Urinary microbiota community composition.
(A) Abundant genus-level phylotypes according to delivery status. (B) Principal coordinates ordination of the weighted UniFrac metric (variance axis 1 = 42.8%, variance axis 2 = 23.1%; p<0.001) for clustering by partitions identified from the Dirichlet multinomial model.
Fig 2
Fig 2. α-diveristy estimates and non-metric dimensional scaling (NMDS) comparing community compostion as meaured by the weighted UniFrac metric and Bray-Curtis dissimialrty for the inferred metagenome for mothers delivering at term (red) or preterm (blue).
(A) Box-plots for α-diveristy estimates (P value >0.76 for all models). (B) NMDS of the weighted UniFrac metric (stress = 0.16; p = 0.78 for clustering by PTB). (C) NMDS of the Bray-Curtis dissimialrity on the inferred metagenome (stress = 0.11; p = 0.82 for clustering by PTB).

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Grant support

This project was supported by The Urban Child Institute (F.T.). The funding sources had no role in the design, implementation and interpretation or in the preparation of the manuscript. The CANDLE study (Director F.T.) was funded by the Urban Child Institute, Memphis, TN. The following are acknowledged for their support of the Microbiome Resource at the University of Alabama at Birmingham: School of Medicine, Comprehensive Cancer Center (P30AR050948), Center for AIDS Research (5P30AI027767), and Center for Clinical Translational Science (UL1TR000165) and Heflin Center.