JU INSIGHT Detection of Bacteria in Bladder Mucosa of Adult Females

By: Alan J. Wolfe, PhD, Loyola University Chicago, Maywood, Illinois; David J. Rademacher, PhD, Loyola University Chicago, Maywood, Illinois, Core Imaging Facility, Loyola University Chicago, Maywood, Illinois; Carine R. Mores, MS, Loyola University Chicago, Maywood, Illinois, Institute of Microbiology and Swiss Institute of Bioinformatics, ETH Zürich, Switzerland; Robert J. Evans, MD, Wake Forest Baptist Medical Center, Winston Salem, North Carolina; Tyler Overholt, MD, Wake Forest Baptist Medical Center, Winston Salem, North Carolina; Thomas Halverson, MPH, Loyola University Chicago, Maywood, Illinois, Northwestern Medicine Delnor Hospital, Geneva, Illinois; Roberto Limeira, MS, Loyola Genomics Facility, Loyola University Chicago, Maywood, Illinois; Catherine Matthews, MD, Wake Forest Baptist Medical Center, Winston Salem, North Carolina; Gopal Badlani, MD, Wake Forest Baptist Medical Center, Winston Salem, North Carolina; Linda Brubaker, MD, MS, University of California San Diego, La Jolla; Stephen J. Walker, PhD, Institute of Microbiology and Swiss Institute of Bioinformatics, ETH Zürich, Switzerland, Wake Forest Institute for Regenerative Medicine, Winston Salem, North Carolina | Posted on: 18 May 2023

Wolfe AJ, Rademacher DJ, Mores CR, et al. Detection of bacteria in bladder mucosa of adult females. J Urol. 2023;209(5):937-949.

Study Need and Importance

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic urological condition. Whether urinary microbiota play an etiological role remains controversial. Most studies assessed the microbiota of IC/BPS patients with voided or catheterized urine as a proxy for bladder urothelium; however, urine may not be a true reflection of bladder microbiota. Direct urothelium assessment, through bladder biopsy, may provide more accurate and clinically relevant information.

What We Found

Using 16S rRNA gene sequencing, we detected bacteria in most urothelial biopsies. The genera are typically detected in bladder urine obtained by transurethral catheter; however, the distribution differed. In urine, Lactobacillus is typically the most prevalent and abundant genus, followed by Gardnerella, Streptococcus, and Staphylococcus. In biopsy tissue, the most prevalent and abundant genus was Staphylococcus, followed by Lactobacillus; Escherichia was prevalent but not abundant. There was no apparent difference between IC/BPS patients and controls. To verify sequencing results, we used a combined fluorescence in situ hybridization and immunohistochemistry imaging, which reproducibly detected 16S rRNA in epithelial cells and shed cells in the urothelium and in lesioned areas and capillary walls in the lamina propria of the biopsy tissue.

Limitations

This small study cohort was all female and did not consider racial/ethnic variability. It does not identify taxa by imaging, limiting the ability to compare imaging and sequencing results. Subsequent studies may benefit from the use of probes for specific taxa.

Interpretation for Patient Care

There is no compelling evidence that bacteria play a significant role in IC/BPS. Etiological discovery should focus elsewhere. While urine obtained by catheter is a noninvasive proxy for bladder microbiota, researchers and clinicians should recognize that compositional distribution may differ. This difference likely results from variability in the degree of association between bacteria that adhere to the surface of the urothelium compared to those that invade.