Date of Award

2017

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Microbiology and Immunology

Abstract

Contrary to dogma, urine is not sterile. Recent discoveries show that the female urinary bladder contains a unique microbiome,with differences in healthy and disease states. This female urinary microbiome (FUM) is distinguishable from vulvo-vaginal contamination; yet, only the few centimeters of the urethra separate these two niches. Recent studies show that the most common bladder organisms are Lactobacillus, Gardnerella, Streptococcus, Corynebacterium, and a diverse group of anaerobes, the same genera commonly found in the vagina. Thus, we asked if the bladder and vaginal microbiomes are interconnected.

Previous work suggests a link between these two niches. The vaginal tract of reproductive age women tends to be dominated by Lactobacillus; however, following menopause, this community becomes more diverse. Our group has seen that asymptomatic women tend to have a Lactobacillus-dominated FUM, whereas older women suffering from urgency urinary incontinence (UUI) tend to have more diverse FUMs with less Lactobacillus. Menopause is a risk factor for urinary disorders, e.g. UUI and urinary tract infection (UTI). Treatment with vaginal estrogen improves UUI symptoms and decreases incidence of recurrent UTIs in this population. It is thought that estrogen's effect on the vagina is mediated by a shift toward a Lactobacillus-dominant microbiome, protecting the bladder against future ascending infections by uropathogens, e.g. E. coli. Because urine was considered sterile, however, no one asked if estrogen treatment also changes the FUM.

Thus, we measured hypoestrogenic UUI women prior to and following 12 weeks of topical estrogen treatment. Prior to treatment, we found that the vaginal and bladder microbiomes of an individual could contain similar organisms with similar structure. Following treatment, however, the two microbiomes became more similar. Many isolates taken from each niche within an individual had highly similar genomes, indicating shared ancestry. Many of these isolates had identical CRISPR arrays, indicating exposure to identical recent phage infections. This implies that these isolates are members of the same lineage. Together, these data suggest that microbial sharing between these two sites is possible. By understanding the FUM, we could develop better diagnostics, identify more effective treatments, and improve the quality of life for millions of women.

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