The Compositional Difference of Bacteria-Derived Extracellular Vesicles in Urine Between Women With and Without Pregnancy Based on Metagenomic Analysis.

Abstract

INTRODUCTION: To evaluate whether bacteria-derived extracellular vesicles (EVs) excrete through the urinary tract and to compare the composition of bacteria-derived EVs in urine between women with and without pregnancy. METHODS: Seventy-three non-pregnant women, and 74 women with pregnancy (39 with normal delivery and 35 with preterm delivery) were enrolled from Dankook University and Ewha Medical Center, respectively. For metagenome analysis, DNA was extracted from urine EVs. 16S rDNA sequencing were conducted using high-throughput sequencing. 16S rDNA sequences were clustered to identify operational taxonomy units (OTUs), and taxonomy was assigned at phylum, class, order, and family levels. Using hierarchical clustering, samples were grouped in terms of the composition of the taxon. RESULTS: Between pregnant and non-pregnant women, a total of 13 taxa show a significant difference in the microbial composition. In particular, Bacillus spp. is the most significantly enriched taxon in pregnant women (45.61%) compared with non-pregnant women (0.12%). On the other hand, Pseudomonas spp. are the most enriched taxon in non-pregnant women (13.23%) compared with pregnant women (4.09%). An OTU that is assigned to family Pseudomonadaceae is also ignificantly enriched in non-pregnant women. Interestingly, Methylobacterium spp. are enriched among both non-pregnant women and pregnant women with preterm delivery, whereas they rarely exist among pregnant women with normal delivery. As for the compositional difference between women with normal and preterm delivery, Ureaplasma spp. and family Veillonelaceae were more frequently detected among women with preterm delivery, compared with those with normal delivery. CONCLUSIONS: The composition of EVs derived from Bacillus spp. increased during pregnancy, whereas those from Pseudomonas spp. increased in non-pregnant women, suggesting that microbe-derived EVs play a key role in the maintenance of homeostasis during pregnancy.