Detection of Bacteria in Bladder Mucosa of Adult Females

Abstract

Purpose:Interstitial cystitis/bladder pain syndrome is a chronic urological condition diagnosed in nearly 8 million females in the United States. Whether urinary microbiota play an etiological role remains controversial. Most studies assessed the microbiota of interstitial cystitis/bladder pain syndrome patients with voided or catheterized urine as a proxy for bladder urothelium; however, urine may not be a true reflection of the bladder microbiota. Bladder biopsy tissue may provide a more accurate, and thus more clinically relevant, picture of bladder microbiota.Materials and Methods:Bladder biopsy tissues were obtained from: (1) 30 females with interstitial cystitis/bladder pain syndrome (18-80 years old) via cystoscopically guided cold-cup biopsy following therapeutic bladder hydrodistention, and (2) 10 non–interstitial cystitis/bladder pain syndrome females undergoing pelvic organ prolapse repair. To detect bacteria, technical duplicates of each RNAlater-preserved biopsy were subjected to 16S rRNA gene sequencing. To visualize bacteria, paraformaldehyde-fixed, paraffin-embedded biopsies were subjected to a combined multiplexed fluorescence in situ hybridization and fluorescence immunohistochemistry assay and confocal microscopy.Results:Bacteria were detected by 16S rRNA gene sequencing in at least 1 technical duplicate of most biopsies. The most abundant genus was Staphylococcus, followed by Lactobacillus; Escherichia was common but not abundant. There was no significant difference between interstitial cystitis/bladder pain syndrome patients and controls (P > .05). Combined fluorescence in situ hybridization and immunohistochemistry reproducibly detected 16S rRNA in epithelial cells and shed cells in the urothelium and lesioned areas and capillary walls in the lamina propria of human bladder biopsy tissue.Conclusions:We conclude that urothelial and urinary microbiota are similar but not identical in adult females.

Secondary Analysis of Interstitial Cystitis/Bladder Pain Syndrome Patients Enrolled in a Recurrent Urinary Tract Infection Prevention Study Provides a Novel Paradigm for Etio-Pathogenesis and Practical Management of This Infection Phenotype

“…It has been hypothesized that some IC/BPS or chronic cystitis-like patients may harbor bacteria within the bladder mucosa [17]. Long-term (up to a year or longer has been advocated), wide-spectrum antibiotics to eradicate the possibility of "embedded" pathogens in the bladder mucosa [23] will lead to potential antibiotic adverse effects and change in the normal microbiome in individual patients as well as increase the spectra of community antibiotic resistance.…”

“…Multiple analyses of the urinary microbiome (using extended culture or non-culture technology) of women with and without IC/BPS have failed to show either a putative micro-organism or bacterial pathogen pattern responsible for the symptoms [16]. However, some believe that some cases of chronic UTI-like symptoms and/or infection-related cases of IC/BPS may be related to sparce bacterial colonies "embedded" in the bladder mucosa [17]. So, the question remains: Are UTIs, either recurrent or chronic UTI (or even UTI in the past), responsible for the development of the symptom complex we call IC/BPS in at least some patients with an infection IC/BPS phenotype?…”

Impact of intravesical Bacillus Calmette-Guérin and chemotherapy on the bladder microbiome in patients with non-muscle invasive bladder cancer

“…A 2023 study by Wolfe et al. compared the microbiota of women with interstitial cystitis to healthy controls ( Wolfe et al., 2023 ). As part of this study, catheterized urine and urothelial biopsy tissue were analyzed using 16S rRNA gene sequencing and compared.…”

This Month in Adult Urology

“…Wolfe et al (page 937) in an international study explore the association of urinary microbiota and interstitial cystitis/bladder pain syndrome. 7 To better understand any potential causative role, the authors assess the microbiome from bladder biopsy tissue. Biopsies were subjected to 16S rRNA gene sequencing and novel imaging techniques including multiplexed fluorescence in situ hybridization.…”