The urinary microbiota of men and women and its changes in women during bacterial vaginosis and antibiotic treatment

Abstract

Background: The urinary microbiota is similarly complex as the vaginal and penile microbiota, yet its role as a reservoir for pathogens and for recurrent polymicrobial biofilm diseases like bacterial vaginosis (BV) is not clear.

Results: Here, we analysed the urinary microbiota of healthy men and women and compared it with that of women during BV and after antibiotic treatment using next-generation sequencing of the 16S rRNA gene V1-V2 regions. Eight different community types, so called urotypes (UT), were identified in healthy humans, all of which were shared between men and women, except UT 7, dominated in relative abundance by Lactobacillus crispatus, which was found in healthy women only. Orally applied metronidazole significantly reduced Shannon diversity and the mean relative abundance of Gardnerella vaginalis, Atopobium vaginae, and Sneathia amnii, while L. iners increased to levels twofold higher than those found in healthy women. Although individual urine microbial profiles strongly responded to the antibiotic, the healthy community could not be restored. The correlation between urinary and vaginal fluid microbiota was generally weak and depending on UT and BV status. It was highest in UT 1 in acute BV (59% of samples), but after metronidazole treatment, only 3 out of 35 women showed a significant correlation between their urinary and vaginal microbiota composition.

Conclusions: Urethra and bladder thus harbor microbial communities distinct from the vagina. The high abundance of BV related species in the urine of both men and women suggests that urine may act as a reservoir of pathogens and contribute to recurrence.

Trial registration: ClinicalTrials.gov, NCT02687789.

Keywords: Antibiotic treatment; Bacterial vaginosis; Healthy urinary microbiome; Urinary microbiota; Urotypes; Vaginal microbiota.

Conflict of interest statement

Ethics approval and consent to participate

The study protocol was approved by the local ethics committees (Bayerische Landesärztekammer, München for the clinical study and Niedersächsische Landesärztekammer, Hannover, for the collection of urine from healthy individuals) and written consent was obtained from all participants. The clinical study was conducted in accordance with the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects. Principles and guidelines for good clinical practice were followed.

Consent for publication

All authors of the manuscript have read and agreed to its content and are accountable for all aspects of the accuracy and integrity of the manuscript in accordance with ICMJE criteria. The article is original, has not already been published in a journal, and is not currently under consideration by another journal.

Competing interests

The authors have read the journal’s policy. The company Dr. August Wolff GmbH developed the pessary against recurrent BV. The study was partially funded through an independent research project by the Bundesministerium für Wirtschaft und Forschung. The authors affiliated with this company (CM, CA) designed the clinical trial, supervised sample distribution to various analytical laboratories and the HZI, and performed statistical analyses of the clinical data. At no point did they interfere with the scientific interpretation of the results. The WO 3191 pessary will not be developed for commercial purposes.

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Figures

Fig. 1

Principle coordinate analyses of the urinary microbiota of healthy men and women (a) and women during acute BV, after metronidazole treatment, and in health (b)

Fig. 2

Rank abundance and Shannon diversity of urinary microbiota. a Dominance plot of cumulated samples from healthy men and women and women during acute BV and after metronidazole treatment. b Shannon indices of all groups. Mean and quartile range are shown. Asterisks indicate significant (p < 0.01) differences

Fig. 3

Individual urinary microbiota of healthy men and women and women during acute BV clustered according to urotypes. Clustering of samples was performed based on the Euclidean distance using the Ward clustering method in R. The 19 most abundant OTUs are shown and all others (boxes above the relative abundance plot. Colored boxes above the abundance plot indicate sample source and grey boxes decode diversity (H′)

Fig. 4

The urinary microbiota during acute BV and after metronidazole treatment. a Principle coordinates analysis of urine samples of women with BV before (red) and after (green) metronidazole treatment. Samples from the same women are connected by a black line. b Mean relative abundance of urine microbiota during acute BV and after metronidazole treatment. The 19 most abundant OTUs are shown and the remaining OTUs are summarized as “others”. c Clustering of urine microbiata after metronidazole treatment. Clustering of samples was performed based on the Euclidean distance using the Ward clustering method in R. Urotypes are indicated. d LefSe analysis of urine microbiota belonging to UT1, UT2, and UT3 before and after metronidazole treatment

Fig. 5

Comparison between urine and vaginal fluid microbiota in acute BV and after metronidazole treatment. a Principal coordinates analysis. b Heatmap of the mean relative abundance of the 20 most abundant taxa. Met metronidazole