First trimester “clean catch” urine and vaginal swab sample distinct microbiological niches

Abstract

ABSTRACT Untreated asymptomatic bacteriuria (ASB) has been associated with adverse pregnancy outcomes. Thus, routine screening by standard urine culture (SUC) and treatment of ASB are currently recommended for all pregnant women. However, SUC often misses microbes detected by expanded quantitative urine culture methods (EQUC) and 16S rRNA gene (amplicon) sequencing. The existence of these microbes (urinary microbiome) challenges the current approach to ASB screening in pregnancy as it is limited by two assumptions: (i) the female bladder is naturally sterile and (ii) SUC identifies all clinically relevant uropathogens. To determine the uniqueness or similarity between urinary and vaginal microbiomes, we performed a prospective observational institutional review board (IRB)-approved cohort study of pregnant women with a singleton pregnancy <14 weeks undergoing routine ASB screening. Consented subjects provided paired midstream voided urine and vaginal swab samples, which were assessed by EQUC and amplicon sequencing. The similarity was determined by Spearman’s correlation; statistical significance was calculated using bootstrap analysis with 1,000 random samples and a significance threshold of P value < 0.001. We used the Bayes theorem to quantify how well the vaginal microbiome could be used as a proxy for a patient’s urinary microbiome and vice versa. Our findings provide evidence that EQUC and amplicon sequencing reveal similar views of urinary and vaginal microbiomes in first trimester pregnant women. However, while vaginal and urinary microbial compositions were significantly correlated for the same individual, they were by no means equivalent. The first trimester urinary and vaginal microbiomes are distinct enough to preclude their use as proxies of each other. IMPORTANCE Untreated asymptomatic bacteriuria (ASB) has been associated with adverse pregnancy outcomes, including pyelonephritis, preterm labor, and low birth weight infants. Thus, routine screening by standard urine culture (SUC) and treatment of ASB are currently recommended for all pregnant women. For this purpose, some researchers claim that vaginal swabs and urine samples can be used as proxies for each other. Because SUC often misses microbes, we used two more sensitive, recently validated detection methods to compare the composition of the urinary and vaginal microbiomes of pregnant females in their first trimester. Both methods yielded similar results. Vaginal and urinary microbial compositions for the same individual were significantly correlated; however, they were not equivalent. We argue that first trimester urinary and vaginal microbiomes are distinct enough to preclude their use as proxies for each other.

Keywords

• asymptomatic bacteriuria
• enhanced culture
• microbiome
• pregnancy
• 16S rRNA gene sequencing
• clinical microbiology